Efficacy and safety of irreversible electroporation in unresectable perihilar cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVES: The prognosis of patients with perihilar-cholangiocarcinoma (PHC) is poor. The only potential curative treatment for patients with PHC is surgical resection, but the large majority present with unresectable disease at diagnosis. The standard of care in patients with unresectable PHC is palliative chemotherapy (CHT).Irreversible electroporation (IRE) has been introduced as a novel ablation technique, working predominantly nonthermal. This review aims to analyse the efficacy and safety of IRE in treating unresectable PHC. METHODS: This systematic review and meta-analysis was performed according to a specific protocol designed a priori, and reported according to the PRISMA. PubMed/MEDLINE, Scopus, and Cochrane CENTRAL were used for the bibliographic research through December 2023. Primary Outcome of interest of our meta-analysis was the mean Overall Survival. Secondary outcomes were Progression-Free Survival and Adverse Event rate. RESULTS: Mean OS is estimated to be 25.49 months (CI 21.47-38.72 I2, 81.37%), PSF 17.86 (CI 13.00-22.72, I2 11.42%), with 12% (CI -7% to 31%, I2 83.57%) of AE incidence. High heterogeneity was found among studies, with no single study fully responsible for it, suggesting high variability among facilities\populations. CONCLUSION: IRE is an effective and relatively safe method in this group of patients. The lack of prospective studies and randomized trials comparing chemotherapy or locoregional treatment with IRE prevents drawing sufficiently robust conclusions. ADVANCES IN KNOWLEDGE: IRE appears is a safe and effective technique for treating unresectable perihilar cholangiocarcinoma.

Burden of delayed discharge on acute hospital medical wards: A retrospective ecological study in Rome, Italy.

INTRODUCTION: Delayed discharge represents the difficulty in proceeding with discharge of patients who do not have any further benefit from prolonged stay. A quota of this problem is related to organizational issues. In the Lazio region in Italy, a macro service re-organization in on the way, with a network of hospital and territorial centers engaged in structuring in- and out- of hospital patient pathways, with a special focus on intermediate care structures. Purpose of this study is to quantify the burden of delayed discharge on a single hospital structure, in order to estimate costs and occurrence of potential resource misplacement. MATERIAL AND METHODS: Observational Retrospective study conducted at the Santo Spirito Hospital in Rome, Italy. Observation period ranged from 1/09/2022, when the local database was instituted, to 1/03/2023 (6 months). Data from admissions records was anonymously collected. Data linkage with administrative local hospital database was performed in order to identify the date a discharge request was fired for each admission. Surgical discharges and Intensive Care Unit (ICU) discharges were excluded from this study. A Poisson hierarchical regression model was employed to investigate for the role of ward, Severity of Disease (SoD) and Risk of Mortality (RoM) on elongation of discharge time. RESULTS: 1222 medical ward admissions were recorded in the timeframe. 16% of them were considered as subject to potentially elongated stay, and a mean Delay in discharge of 6.3 days (SD 7.9) was observed. DISCUSSION AND CONCLUSIONS: Delayed discharge may cause a "bottleneck" in admissions and result in overcrowded Emergency Department, overall poor performance, and increase in overall costs. A consisted proportion of available beds can get inappropriately occupied, and this inflates both direct and indirect costs. Clinical conditions on admission are not a good predictor of delay in discharge, and the root causes of this phenomenon likely lie in organizational issues (on structure\system level) and social issues (on patient's level).

Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study.

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable < 50 copies/ml switching to BIC/FTC/TAF. A previous 12-month monitoring was available, and the factors correlated with treatment efficacy. This retrospective multicenter study included PLWH who switched to BIC/FTC/TAF in the period of 2019-2022, and who were HBsAg and HCV RNA negative. The follow-up study times were 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months after the switch (T0). Survival analysis with multiple-failure-per-subject design, Kaplan-Meier survival estimates, multivariate analysis of variance, multilevel linear regression, and a hierarchical ordered logistic model were applied. A total of 329 PLWH had plasma HIV RNA which was either undetectable or detectable at <50 copies/mL at T0, and 197 responded to all inclusion criteria: M/F 140/57; the median CD4+ cell count was 677 cells/mm3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF.

Intra- and Extra-Hospitalization Monitoring of Vital Signs-Two Sides of the Same Coin: Perspectives from LIMS and Greenline-HT Study Operators.

BACKGROUND: In recent years, due to the epidemiological transition, the burden of very complex patients in hospital wards has increased. Telemedicine usage appears to be a potential high-impact factor in helping with patient management, allowing hospital personnel to assess conditions in out-of-hospital scenarios. METHODS: To investigate the management of chronic patients during both hospitalization for disease and discharge, randomized studies (LIMS and Greenline-HT) are ongoing in the Internal Medicine Unit at ASL Roma 6 Castelli Hospital. The study endpoints are clinical outcomes (from a patient's perspective). In this perspective paper, the main findings of these studies, from the operators' point of view, are reported. Operator opinions were collected from structured and unstructured surveys conducted among the staff involved, and their main themes are reported in a narrative manner. RESULTS: Telemonitoring appears to be linked to a reduction in side-events and side-effects, which represent some of most commons risk factors for re-hospitalization and for delayed discharge during hospitalization. The main perceived advantages are increased patient safety and the quick response in case of emergency. The main disadvantages are believed to be related to low patient compliance and an infrastructural lack of optimization. CONCLUSIONS: The evidence of wireless monitoring studies, combined with the analysis of activity data, suggests the need for a model of patient management that envisages an increase in the territory of structures capable of offering patients subacute care (the possibility of antibiotic treatments, blood transfusions, infusion support, and pain therapy) for the timely management of chronic patients in the terminal phase, for which treatment in acute wards must be guaranteed only for a limited time for the management of the acute phase of their diseases.

Improving clinical diagnostic accuracy and management of False penile fractures characterizing typical clinical presentation: a systematic review and meta-analysis.

PURPOSE: False penile fractures (FPF) represent a rare sexual emergency characterized by blunt trauma of penis in the absence of albuginea's injury, with or without lesion of dorsal penile vein. Their presentation is often indistinguishable from true penile fractures (TPF). This overlapping of clinical presentation, and lack of knowledge about FPF, can lead surgeons often to proceed directly to surgical exploration without further examinations. The aim of this study was to define a typical presentation of false penile fractures (FPF) emergency, identifying in absence of "snap" sound, slow detumescence, penile shaft ecchymosis, and penile deviation main clinical signs. METHODS: We performed a systematic review and meta-analysis based on Medline, Scopus and Cochrane following a protocol designed a priori, to define sensitivity of "snap" sound absence, slow detumescence and penile deviation. RESULTS: Based on the literature search of 93 articles, 15 were included (73 patients). All patients referred pain, most of them during coitus (n = 57; 78%). Detumescence occurred in 37/73 (51%), and all patients described detumescence occurrence as "slow". The results show that single anamnestic item have a high-moderate sensibility in the diagnosis of FPF, and the highest sensitive item was penile deviation (sensibility = 0.86). However, when more than one item is present, overall sensitivity increases greatly, closing to 100% (95% Confidence Interval 92-100). CONCLUSION: Surgeons can consciously decide between additional exams, a conservative approach, and rapid intervention using these indicators to detect FPF. Our findings identified symptoms with excellent specificity for FPF diagnosis, giving clinicians more useful tools for making decisions.

Polypharmacy Management in a Gender Perspective: At the Heart of the Problem: Analysis of Major Cardiac Diseases, SARS-CoV-2 Affection and Gender Distribution in a Cohort of Patients in Internal Medicine Ward.

BACKGROUND: COVID-19 patients with any pre-existing major cardio-vascular disease (CVD) are at the highest risk of viral infection and of developing severe disease. The pathophysiological mechanism is characterized by the viral link to angiotensin-converting enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and the inflicting of direct damage to the myocardium, the induction of microthrombosis, and the initiation of alterations in oxygen diffusion. The aim of the study is to analyze the clinical course and outcomes in patients (gender-stratified) with pre-existing major CVD. METHODS: Out of the 1833 (973 M/860 F) patients admitted to the Internal Medicine COVID-19 Unit of "Castelli Hospital", Lazio, Italy, from 1 January 2021 to 31 December 2021, 600 patients (320 M/280 F) with a mean age of 77 (78.6 M/75.1 F) previously had CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. RESULTS: All of the CVD COVID-19 patients underwent non-invasive ventilation (NIV). CVD was linked with increased LOS (21 days F/22 M) compared to no CVD (19 days). In total, 32.7% of total patients had major CVD. CONCLUSIONS: Timely identification and evaluation of patients with pre-existing major CVD are fundamental for adequate treatment based on gender, severity, state of illness and for risk reduction.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

Appropriateness of frequent use of emergency departments: A retrospective analysis in Rome, Italy.

Background: Frequent users (FUs) are patients who repeatedly and inappropriately visit the emergency department (ED) for low-grade symptoms that could be treated outside the hospital setting. This study aimed to investigate the phenomenon of the FU in Rome by profiling such users and analyzing ED attendance by FUs. Methods: The analysis was carried out for attendance in 2021 at 15 EDs in the Local Health Authority Roma 1 geographical area. A digital app collected data, including information on the following variables: number of attendance, demographic characteristics, emergency medical service (EMS) usage, triage code, and appropriateness of attendance. COVID-19 diagnosis was also studied to analyze any possible influence on ED attendance. Differences between FUs and non-FUs were investigated statistically by t-test and chi-square test. Univariate analysis and multivariable logistic regression were performed to analyze the associated factors. Results: A total of 122,762 ED attendance and 89,036 users were registered. The FU category represented 2.9% of all users, comprising 11.9% of total ED attendance. There was a three times higher frequency of non-urgent codes in attendance of FU patients (FU: 9.7%; non-FU: 3.2%). FUs were slightly more likely to have used the EMS (13.6% vs. 11.4%) and had a lower frequency of appropriate ED attendance (23.8% vs. 27.0%). Multivariate logistic analysis confirmed a significant effect of triage code, gender, age, EMS usage, and COVID-19 diagnosis for the appropriateness of attendance. The results were statistically significant (p < 0.001). Conclusion: The FU profile describes mostly non-urgent and inappropriate attendance at the ED, including during the COVID-19 pandemic. This study represents an important tool for strengthening preventive policies outside the hospital setting. The Italian National Recovery and Resilience Plan represents an excellent opportunity for the development of new strategies to mitigate the phenomenon of FUs.

Unemployment Status Subsequent to Cancer Diagnosis and Therapies: A Systematic Review and Meta-Analysis.

The purpose of our study is to examine whether cancer and treatments are associated with job loss or changes in employment status. Eight prospective studies were included in the systematic review and meta-analysis, with a population aged 18-65 years, analyzing treatment regimen and psychophysical and social status in post-cancer follow-up of at least 2 years. In the meta-analysis, a comparison was made between recovered unemployed cases and cases from a standard reference population. Results are summarized graphically using a forest plot. We showed that cancer and subsequent treatment are risk factors for unemployment with an overall relative risk of 7.24 (lnRR: 1.98, 95% CI: 1.32-2.63) or for change in employment status. Individuals undergoing chemotherapy and/or radiation treatment and those with brain and colorectal cancers are more likely to develop disabilities that negatively affect the risk of unemployment. Finally, variables such as low level education, female sex, older age, and being overweight before starting therapy are associated with higher risk of unemployment. In the future, it will be necessary for people with cancer to have access to specific health, social welfare, and employment support programs. In addition, it is desirable that they become more involved in their choice of therapeutic treatment.

Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis.

BACKGROUND: The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). METHOD: We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. RESULTS: Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn's disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. CONCLUSIONS: This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

This article is a systematic review with meta-analysis of randomized clinical trials involving inflammatory bowel disease patients treated with vitamin D supplementation, compared with placebo. We aim to assess the risk of clinical relapse or disease activity among these patients.

Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

(1) Introduction: Inflammatory Bowel Disease (IBD) patients may benefit from cannabinoid administration supplementary therapy; currently no consensus on its effect has been reached. (2) Methods: a systematic review of RCTs on cannabinoid supplementation therapy in IBD has been conducted; data sources were MEDLINE, Scopus, ClinicalTrials. (3) Results: out of 974 papers found with electronic search, six studies have been included into the systematic review, and five of them, for a grand total of 208 patients, were included into the meta-analysis. (4) Conclusions: cannabinoid supplementation as adjuvant therapy may increase the chances of success for standard therapy of Crohn's Disease during the induction period; no statement on its potential usage during maintenance period can be derived from retrieved evidence. Its usage in Ulcerative Colitis is not to be recommended. If ever, low-dose treatment may be more effective than higher dosage. Mean CDAI reduction was found stronger in patients treated with cannabinoids (mean CDAI reduction = 36.63, CI 95% 12.27-61.19) than placebo. In future studies, it is advisable to include disease activity levels, as well as patient-level information such as genetic and behavioral patterns.

Emergency Medical Services Calls Analysis for Trend Prediction during Epidemic Outbreaks: Interrupted Time Series Analysis on 2020-2021 COVID-19 Epidemic in Lazio, Italy.

(1) Background: During the COVID-19 outbreak in the Lazio region, a surge in emergency medical service (EMS) calls has been observed. The objective of present study is to investigate if there is any correlation between the variation in numbers of daily EMS calls, and the short-term evolution of the epidemic wave. (2) Methods: Data from the COVID-19 outbreak has been retrieved in order to draw the epidemic curve in the Lazio region. Data from EMS calls has been used in order to determine Excess of Calls (ExCa) in the 2020−2021 years, compared to the year 2019 (baseline). Multiple linear regression models have been run between ExCa and the first-order derivative (D') of the epidemic wave in time, each regression model anticipating the epidemic progression (up to 14 days), in order to probe a correlation between the variables. (3) Results: EMS calls variation from baseline is correlated with the slope of the curve of ICU admissions, with the most fitting value found at 7 days (R2 0.33, p < 0.001). (4) Conclusions: EMS calls deviation from baseline allows public health services to predict short-term epidemic trends in COVID-19 outbreaks, and can be used as validation of current data, or as an independent estimator of future trends.

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients.

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th−25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules.

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.

Burden of COVID-19 on Italian Internal Medicine Wards: Delphi, SWOT, and Performance Analysis after Two Pandemic Waves in the Local Health Authority "Roma 6" Hospital Structures.

Background: COVID-19 causes major changes in day-to-day hospital activity due to its epidemiological characteristics and the clinical challenges it poses, especially in internal medicine wards. Therefore, it is necessary to understand and manage all of the implicated factors in order to maintain a high standard of care, even in sub-par circumstances. Methods: This was a three-phase, mixed-design study. Initially, the Delphi method allowed us to analyze the causes of poor outcomes in a cohort of an aggregate of Italian COVID-19 wards via an Ishikawa diagram. Then, for each retrieved item, a score was assigned according to a pros/cons, opportunities/threats system. Scores were also assigned according to potential value/perceived risk. Finally, the performances of MCs (Medicine-COVID-19 wards) and MCFs (Medicine-COVID-19-free: Internal Medicine wards) units were represented via a Barber's nomogram. Results: MCFs hospitalized 790 patients (-23.90% compared to 2019 Internal Medicine admissions). The main risk factors for mortality were patients admitted from local facilities (+7%) and the presence of comorbidities (>3: 100%, ≥5: 24.7%). A total of 197 (25%) patients were treated with non-invasive ventilation (NIV). The most deaths (57.14%) occurred in patients admitted from local facilities. Conclusions: Medicine-COVID-19 wards show higher complexity and demand compared to non-COVID-19 ones and they are comparable to sub-intensive therapy wards. It is necessary to promote the use of NIV in such settings.

Can risk be predicted? An umbrella systematic review of current risk prediction models for cardiovascular diseases, diabetes and hypertension.

OBJECTIVE: To provide an overview of the currently available risk prediction models (RPMs) for cardiovascular diseases (CVDs), diabetes and hypertension, and to compare their effectiveness in proper recognition of patients at risk of developing these diseases. DESIGN: Umbrella systematic review. DATA SOURCES: PubMed, Scopus, Cochrane Library. ELIGIBILITY CRITERIA: Systematic reviews or meta-analysis examining and comparing performances of RPMs for CVDs, hypertension or diabetes in healthy adult (18-65 years old) population, published in English language. DATA EXTRACTION AND SYNTHESIS: Data were extracted according to the following parameters: number of studies included, intervention (RPMs applied/assessed), comparison, performance, validation and outcomes. A narrative synthesis was performed. Data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. STUDY SELECTION: 3612 studies were identified. After title/abstract screening and removal of duplicate articles, 37 studies met the eligibility criteria. After reading the full text, 13 were deemed relevant for inclusion. Three further papers from the reference lists of these articles were then added. STUDY APPRAISAL: The methodological quality of the included studies was assessed using the AMSTAR tool. RISK OF BIAS IN INDIVIDUAL STUDIES: Risk of Bias evaluation was carried out using the ROBIS tool. RESULTS: Sixteen studies met the inclusion criteria: six focused on diabetes, two on hypertension and eight on CVDs. Globally, prediction models for diabetes and hypertension showed no significant difference in effectiveness. Conversely, some promising differences among prediction tools were highlighted for CVDs. The Ankle-Brachial Index, in association with the Framingham tool, and QRISK scores provided some evidence of a certain superiority compared with Framingham alone. LIMITATIONS: Due to the significant heterogeneity of the studies, it was not possible to perform a meta-analysis. The electronic search was limited to studies in English and to three major international databases (MEDLINE/PubMed, Scopus and Cochrane Library), with additional works derived from the reference list of other studies; grey literature with unpublished documents was not included in the search. Furthermore, no assessment of potential adverse effects of RPMs was carried out. CONCLUSIONS: Consistent evidence is available only for CVD prediction: the Framingham score, alone or in combination with the Ankle-Brachial Index, and the QRISK score can be confirmed as the gold standard. Further efforts should not be concentrated on creating new scores, but rather on performing external validation of the existing ones, in particular on high-risk groups. Benefits could be further improved by supplementing existing models with information on lifestyle, personal habits, family and employment history, social network relationships, income and education. PROSPERO REGISTRATION NUMBER: CRD42018088012.

On the thermal shock resistance and mechanical properties of novel unidirectional UHTCMCs for extreme environments.

Aerospace provides a strong driving force for technological development. Recently a novel class of composites for harsh environments, based on ultra-high temperature ceramic composites reinforced with continuous fibers (UHTCMC), is being developed. The goal of this work is to overcome the current data patchwork about their microstructural optimization and structural behavior, by showing a consistent mechanical characterization of well-defined and developed UHTCMCs based on ZrB2-matrix. The obtained composites have a density of 3.7 g/cm3 and porosity of less than 10%. The flexural strength increased from 360 to 550 MPa from room temperature to 1500 °C, showing a non-brittle behaviour. The composites were able to sustain a thermal shock severity as high as 1500 °C. The maximum decrease of strength at 1400 °C was 16% of the initial value, indicating that the samples could be shocked at even higher temperature. Flexural strength, Young's modulus and coefficient of thermal expansions (CTE) of the composites were measured both along transverse and longitudinal direction and correlated to the microstructural features. The presented microstructural and mechanical characterization well defines the potentiality of the UHTCMCs and can be used as reference for the design and development of novel thermal protection systems and other structural components for harsh environments.