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Background and aim: On January 9, 2020, the World Health Organization (WHO) declared that Chinese health authorities had identified a new coronavirus strain never before isolated in humans, the 2019-nCoV later redefined SARS-CoV-2, that still today represent a public health problem. The present survey started on 10 February 2020 with the aim of a) assessing the risk perception in healthcare workers and young students, following the evolution of attitudes, perception and knowledge over time, b) provide useful information to the general population during survey. Results: A study sample consisting of 4116 Italian in-dividuals of both sexes was enrolled. High levels of risk perception, low perception of self-efficacy and low levels of knowledge scores (24.55 ± 5.76 SD) were obtained indicating the need for continuous population monitoring as well as further communication strategies carried out at institution levels. Conclusion: The results of the present study could help public health authorities in carrying out informative campaigns for general population and could be an important tool in evaluating public knowledge and misperceptions during the management of the COVID-19. (www.actabiomedica.it).

Refugees are a growing population in the EU-27 area with specific health needs that are to be addressed in the most rapid and effective way at their arrival in the host country. Screening for Hepatitis B Virus infection is offered to specific categories and it could be useful and effective to extend its indications. The aim of this study was to define the epidemiological profile regarding Hepatitis B Virus infection in re-fugees hosted in the Asylum Seekers Centers of Verona (Italy), diagnosed with latent tuberculosis infection and eligible for chemoprophylaxis.We conducted a retrospective study in 715 refugees diagnosed with latent tuberculosis infection from January 1st, 2015 to December 31st, 2017. Screening for Hepatitis B Virus infection was offered to la-tent tuberculosis infection patients who were due to commence treatment. Subjects were tested for Hepatitis B surface Antigen and Hepatitis B core antigen total antibodies. None of the screened patients reported previous vaccination for hepatitis B.Among the 715 refugees diagnosed with latent tuberculosis infection, 593 were eligible for treatment for latent tuberculosis infection. Of these, 211 (35.6%) accepted to be screened for Hepatitis B Virus infection. One hundred and ninety-five of the 211 (92.4%) came from African countries, and 16 (7.6%) from Asia; the majority (80.9%) were males. Median age was 23 years (95% CI 22-24). Of the 211, 58 individuals (27.5%) were Hepatitis B surface Antigen and Hepatitis B core antigen total antibodies positive; 74 (35.1%) were Hepatitis B surface Antigen negative and Hepatitis B core antigen total antibodies positive; and 79 (37.4%) were Hepatitis B surface Antigen and Hepatitis B core antigen total antibodies negative. Male gender and African origin were associated with a lower probability of being Hepatitis B surface Antigen- and Hepatitis B core antigen total antibodies-negative.Screening for Hepatitis B Virus is of paramount importance not only for the control and prevention of infection, but also in terms of long-term healthcare issues. Making screening more systematic can have an important impact on public health, while always considering cost-effectiveness and promotion of awareness among ethnic groups in order to gain their compliance to treatment/vaccination.

Despite the scientific consensus about vaccines safety and effectiveness, there is still a discrepancy between scientific evidence and perception by the general population. The "VaccinarSì" portal was created in 2013 by Italian specialists in Public Health to provide evidence-based information regarding vaccination.The purpose of this study was to analyse the web traffic on "VaccinarSì" platform during a six-year period (May 8, 2013-May 8, 2019). Moreover, we compared the first six-month with the last six-month period of the website activity, to identify potential areas of improvements.This is a descriptive study using Google Analytics data. We collected data regarding the following: total number of sessions to the portal, total number of pages viewed, total number of users and the number of new visitors, geographical locations and demography of users as well as user access mode (type of device used and way of access). We also collected some data that were informative about the possibility to infer the level of visitors' engagement with the portal, such as thee number of returning users, bounce rate, number of pages visited per session and mean session duration.Throughout the relevant period, the portal has consistently increased its popularity, with a remarkable increment of monthly connections (ending up to more than 80,000/month) from all over Italy. Visitors were mainly female (71.1%), aged between 25 and 44 years (64.7%). Healthcare professionals were responsible for a considerable proportion of accesses (50.6%). The mobile has become the dominant device used to access the portal, accounting for 77.8% of total connection in the last six months. Similarly, in the last period, organic search accounted for 92% of all connections. Measles and MPR vaccine, as well as chickenpox and hexavalent vaccine, have remained the most appealing topics of interest among visitors over the years. The page that attracted more visitors over the six years was "real risks and benefits of vaccination", accounting for 5.67% of total sessions with a high mean duration spent of 05:08 minutes.During the six years of activity, overall, the level of users' engagement with the portal has dropped with an increased bounce rate and a lower average number of pages visited per session and a lower mean duration of each connection. The lowest engagement involved connections accessed through mobile devices. Results helped "Vaccinarsi" developers to speculate about future strategies to further increase the platform popularity and optimize visitors' engagement.

The hard-to-reach populations, including the homeless, are particularly vulnerable to the development of active tuberculosis. According to the World Health Organization, tuberculosis rates among the homeless in industrialized Countries are up to 20 times higher if compared with the general popula-tion, representing a relevant public health problem. The aim of our study was to describe the results of an active tuberculosis screening applied in order to find out suspected active TB cases among the homeless in Verona.As part of a partnership between the non-profit association Medici per la Pace and one of the Local Health Units of Veneto Region (ULSS 9 Scaligera) in 2018, a tuberculosis screening, based on thoracic radiographs, was offered to the homeless guests of two Verona's soup kitchens.The studied population included 139 people, and three cases of suspected active tuberculosis, all in males, were observed. Among these, two received a diagnostic confirmation of active tuberculosis (a prevalence of 1.44% - CI: 0,17 - 5,1). Moreover, radiographic patterns of tuberculosis aftermaths were found in six additional subjects.Interventions specifically dedicated to hard-to-reach populations, can be useful in identifying tuberculosis active cases and controlling the disease in low tuberculosis burden countries. In particular, the active research of subjects, the screening carried out with mobile X-ray, and also the constant caring of the patients with active disease, could be the right method to keep under control this relevant public health problem.

Seasonal influenza is a highly contagious infection that might lead to serious clinical complications and incurs a conspicuous socio-economic impact. Influenza vaccination is currently recommended only for specific groups of healthy adults (such as healthcare workers) even though it was demonstrated to be effective in reducing absenteeism and decreased workers' productivity during flu epidemic period. The main purpose of this study is to analyse the extent of absences due to illness following a voluntary flu immunization program among the Komatsu Italia Manufacturing company's personnel during the flu season 2017-2018. Secondly, we aimed at performing a cost-benefit analysis of the vaccination campaign from the company's perspective.This is an observational cohort study conducted during the period between the 14th week of 2017 and the 13th week of 2018 (from 03/04/2017 to 01/04/2018). The study population was the personnel of Komatsu Italia Manufacturing S.p.A. on duty during the study period.For each subject the following data were collected: sex, date of birth, professional profile, seasonal influenza immunization status and sick-leave days. Sick-leave days were compared among the influenza epidemic period and the previous one between vaccinated and unvaccinated and any difference in days of absence was considered to be caused by seasonal influenza.Out of 408 employees, 60 (14.7%) accepted the voluntary influenza vaccination. In multivariate analysis (logistic model) an age ≥ 50 years was the only predictor for vaccination acceptance (ORM 3.11 p0.001). During the flu period, the monthly mean of sick-leave days per employee was significantly lower among the vaccinated than the unvaccinated, respectively of 0.328 days/person vs 0.752 days/person (p = 0.022). Unvaccinated employees reported a higher average of sick-leave days during the flu period compared to the previous non-influenza period (0.752 days/month/person vs 0.337 days/month/person p0.001). The monthly mean cost for sickness absences per employee was significantly higher for an unvaccinated subject compared to one vaccinated, respectively € 129.00 and € 54.00 (p = 0.028). The overall net saving estimated was € 314.00 per person vaccinated.Influenza vaccination proved to be an extraordinary preventive tool and a cost-effective intervention. However, influenza immunization seems to be unappealing among healthy adults and higher flu vaccination coverages could be achieved through educational interventions possibly addressing young employees who showed little interest in vaccination. Finally, among health promotion interventions, companies should point out the importance of flu vaccination both for the individual wellbeing and the company environment.

Although hospital hygiene has a long history in Italy it is necessary to reflect about it because of the innovation in healthcare systems and because of the evolution due to European Union related activities. Different traditions exist in European countries about hospital hygiene and European Centre for Disease Prevention and Control (ECDC) adopted the term of "infection control and hospital hygiene" which includes all the engaged European healthcare professionals. We propose to modify hospital hygiene as "healthcare organisation hygiene" in order to focalise the attention to all care settings not only hospitals and to adopt the following definition: "all activities aimed to guarantee, in an appropriate, scientifically sound and efficient way, that structures and processes support healthcare practices in a safe comfortable and healthy environment both for patients, caregivers and healthcare workers". Hospital hygiene and its professionals, besides the long tradition, still remain a relevant pillar in guaranteeing quality and safety of healthcare in Italy.

Healthcare-Associated Infections are a great concern for worldwide healthcare systems and represent a considerable threat to patient safety, leading to adverse clinical outcomes. A defined panel of indicators represents a key element to guide Healthcare Organizations towards identification of main gaps, implementation of effective actions and continuous improvements on Healthcare-Associated Infections prevention and control activities. A review on accreditation systems conducted by the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene Preventive Medicine and Public Health revealed a substantial heterogeneity of implemented standards and led to the development of a core set of indicators and requirements for Healthcare-Associated Infections' prevention and control within the hospital setting. The main aim of the study was to test the feasibility of the Healthcare-Associated Infections' prevention and control within the hospital setting tool to calculate performance scores on a sample of Italian Healthcare Organizations and to identify major critical issues. The potential benefits of the possibility of future implementation of the tool within Institutional Accreditation Programs is discussed.Cross sectional pilot survey.The Healthcare-Associated Infections' prevention and control within the hospital setting included 96 criteria and 20 key areas including an area for outcomes indicators. For applicable criteria, standards fulfilment was evaluated according to a 4 point Likert scale. A composite score was calculated for each Healthcare Organization and five performance levels were identified. Data were further analysed by computing performance scores at the level of each area and requirement.20 Healthcare Organizations agreed to take part in this pilot study including two rehabilitative Healthcare Organizations. Among the whole sample a mean of 12.20% of requirements resulted not fulfilled, leaving space for further improvements. Critical areas were easily identified and the instrument was able to capture substantial differences between Healthcare Organizations. Only a few number of standards resulted "Not Applicable" (Mean = 4.71%) and most of them regarded Rehabilitative Healthcare Organizations. Mean composite performance index resulted 74.06% (SD = 16.96, range 36.30 - 94.27%); area of outcome indicators obtained a mean score of 56.17.The Healthcare-Associated Infections' prevention and control within the hospital setting resulted an useful tool to assess Healthcare Organizations' performance in the field of Healthcare-Associated Infections prevention and control and to identify necessary actions for further improvements. The distribution of total scores by Healthcare Organizations showed a high heterogeneity. Implementation of the Healthcare-Associated Infections' prevention and control within the hospital setting tool as an institutional accreditation tool may help to drive the required harmonization at a national level of Healthcare-Associated Infections management and control strategies and overcome current substantial regional differences.

Background Characteristics, associated factors, and survival probability of toxoplasmic encephalitis (TE) in the era of advanced highly active antiretroviral therapy (HAART) have not been fully clarified. Methods Data for 205 individuals with acquired immunodeficiency syndrome (AIDS)-related TE were derived from the Italian Registry Investigative NeuroAIDS database, and the cases were studied longitudinally to evaluate prevalence, clinical characteristics, and survival. Moreover, the relationship between the occurrence of TE and exposure to antiretroviral therapy and to TE prophylaxis was evaluated. Results With an overall prevalence of 26%, TE represented the most frequent neurological disorder in the cohort. Female sex, severe immunodeficiency, and absence of primary TE prophylaxis significantly increased the risk of TE, and previous exposure to antiretroviral therapy reduced the probability of disease occurrence. Thirty-six percent of patients who had received antiretroviral therapy developed TE, although in most of these cases, the patient experienced failure of antiretroviral therapy. Of note, 66% of patients who had experienced antiretroviral therapy did not receive prophylaxis for TE at TE diagnosis. The 1-year probability of that infection with human immunodeficiency virus (HIV) would progress or that death would occur after TE was 40% and 23%, respectively. Cognitive symptoms, low CD4(+) cell count, not receiving HAART after TE, and initiating HAART >2 months after TE diagnosis were all significantly associated with an increased probability of progression of HIV infection. Not receiving HAART after diagnosis negatively affected survival. Conclusions TE remains a highly prevalent disorder of the central nervous system, even in the late HAART era, particularly among severely immunosuppressed patients and in absence of prophylaxis. Considering that persons with TE have a high probability of early death, prophylaxis should be maintained in immunosuppressed patients who experience failure of antiretroviral therapy, and HAART should be initiated as soon as possible after TE diagnosis.

MDM4 is a key regulator of p53, whose biological activities depend on both transcriptional activity and transcription-independent mitochondrial functions. MDM4 binds to p53 and blocks its transcriptional activity; however, the main cytoplasmic localization of MDM4 might also imply a regulation of p53-mitochondrial function. Here, we show that MDM4 stably localizes at the mitochondria, in which it (i) binds BCL2, (ii) facilitates mitochondrial localization of p53 phosphorylated at Ser46 (p53Ser46(P)) and (iii) promotes binding between p53Ser46(P) and BCL2, release of cytochrome C and apoptosis. In agreement with these observations, MDM4 reduction by RNA interference increases resistance to DNA-damage-induced apoptosis in a p53-dependent manner and independently of transcription. Consistent with these findings, a significant downregulation of MDM4 expression associates with cisplatin resistance in human ovarian cancers, and MDM4 modulation affects cisplatin sensitivity of ovarian cancer cells. These data define a new localization and function of MDM4 that, by acting as a docking site for p53Ser46(P) to BCL2, facilitates the p53-mediated intrinsic-apoptotic pathway. Overall, our results point to MDM4 as a double-faced regulator of p53.

A wild-type (wt) p53 gene characterizes thyroid tumors, except for the rare anaplastic histotype. Because p53 inactivation is a prerequisite for tumor development, alterations of p53 regulators represent an alternative way to impair p53 function. Indeed, murine double minute 2 (MDM2), the main p53 negative regulator, is overexpressed in many tumor histotypes including those of the thyroid. A new p53 regulator, MDM4 (a.k.a. MDMX or HDMX) an analog of MDM2, represents a new oncogene although its impact on tumor properties remains largely unexplored. We estimated levels of MDM2, MDM4, and its variants, MDM4-S (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary thyroid carcinomas (PTC), characterized by wt tumor protein 53, in comparison to matched contra-lateral lobe normal tissue. Further, we evaluated the association between expression levels of these genes and the histopathological features of tumors. Quantitative real-time polymerase chain reaction revealed a highly significant downregulation of MDM4 mRNA in tumor tissue compared to control tissue (P

In psychiatry, individual‐based registries have provided key information on risks and benefits associated with the use of psychotropic drugs but they have rarely been employed for monitoring and evaluating the everyday prescribing of psychopharmacological treatments. This article describes the cultural background that gave impetus to the idea of registering all prescriptions of psychotropic drugs dispensed by physicians working in the South Verona community mental health service, and presents the methodology employed to develop such a registry in a community psychiatric service where a psychiatric case register (PCR) has been operating since 1978. We developed a registry including every patient receiving psychotropic medications in ordinary practice. This registry is linked to the PCR in order to obtain data on social and demographic characteristics, clinical symptoms, diagnosis, use of services, and outcomes. No exclusion criteria are allowed — anyone receiving treatment is automatically included. This system, which can link drug and service‐use data with hard outcome indicators, can generate information on the proportion of subjects discontinuing treatment, switching medication because of side‐effects, recovery or inefficacy, as well as on the proportion of subjects failing to return to the physician, and the proportion of patients who improve. The innovative aspect of this approach is that this registry is developed, organized and used by physicians interested in monitoring their clinical practice and in providing patients, relatives and the public with accurate information on drug use in their specific context of care. Copyright © 2005 John Wiley & Sons, Ltd.

Clinical biophysics investigates the relationship between non-ionizing physical energy and the human body. Although several types of electrical stimulation devices have received US FDA approval for orthopaedic application, the use of Pulsed Electromagnetic Field (PEMFs) play a central role in joint biophysics. This narrative review aims to summarize the current evidences on the efficacy of PEMF-therapy in the treatment of knee articular diseases. Preclinical studies have assessed the effects of PEMFs on chondrocytes, synoviocytes, articular cartilage explants and animal models, showing positive effects of PEMF-therapy on cells proliferation, extracellular matrix (ECM) production, chondrocytes apoptosis and inflammatory cytokines down-regulation. Currently, PEMF-therapy is a valid option in the conservative management of several knee articular diseases, including early OA, patellofemoral pain syndrome and SONK. PEMFs could be also used as an adjunct after an arthroscopic knee procedure or TKA implantation, in order to control the joint post-operative inflammatory state.

A reduction in the use of opioids by older adult patients could reduce unpleasant side effects for them. During general anesthesia, binaural beat (BB) listening has been found to reduce intraoperative fentanyl consumption as well as postoperative pain scores and discharge time. Auditory BBs are a perceptual phenomenon occurring when tones of 2 slightly different frequencies are presented simultaneously and separately to each ear.The study intended to evaluate the ability of BBs, as a nonpharmacological premedication, to reduce postoperative morphine consumption in older adults undergoing total knee replacement surgery and to modify the levels of anxiety and feelings of pain that patients experience.The research team designed a prospective, single-center, randomized controlled study.The study was conducted in the Orthopedic Department of the Santa Maria Maddalena Hospital (Volterra [Pisa], Italy).Forty older adults at the hospital who were undergoing total knee joint replacement with spinal anesthesia participated in the study.The study included 2 groups (n = 20 each), one receiving BBs stimulation with frequencies of 256 Hz in one ear and 260 Hz in the opposite ear producing a BB of 4 Hz (intervention group), and the other receiving acoustical stimulation at 256 Hz in both ears (control group). BBs, or acoustical stimulation, were administered before the surgical procedure. Both acoustical stimuli, generated with the Gnaural program, were delivered through stereo headphones connected to a laptop in the preoperative holding area.The study measured postoperative, cumulative, self-administered morphine consumption, in mg, through a patient-controlled analgesia device. Feelings of anxiety were also assessed using the State-Trait Anxiety Inventory, and feelings of pain were measured every 8 h during the first postoperative day using a numerical rating scale.Patients who received the intervention, consumed almost half of the dosage of morphine during the first postoperative day when compared with the control group's consumption, 5.75 mg ± 5.25 vs 11.85 mg ± 7.71, respectively. The consumption did not correlate to anxiety measures. Regarding pain perception, no differences between the groups were captured.BB stimulation before surgery can be successfully used as a nonpharmacological treatment to reduce morphine consumption in older adults who undergo knee replacement. The use of a noninvasive, safe, and inexpensive BB intervention can result in a positive effect on patients' postoperative recovery.

© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students.

The COVID-19 pandemic has had a severe psychosocial impact on healthcare workers (HCWs). This systematic review and meta-analysis aimed at evaluating the association between individual features and depressive symptoms reported by HCWs during the pandemic. We searched Medline, Embase, and PsycInfo up to 23 June 2020. We included cross-sectional studies testing the association between individual correlates and depressive symptoms in HCWs during the SARS-CoV-2 outbreak. Fourteen studies met inclusion criteria, involving 14,173 HCWs (3,070 with depressive symptoms). Women (OR = 1.50; 95 %CI: 1.28–1.76; I2 = 40.0 %), individuals with suspected/confirmed COVID-19 (OR = 2.10; 95 %CI: 1.64–2.69; I2 = 0 %), and those with an infected family member or friend (OR = 1.67; 95 %CI: 1.37–2.04; I2 = 0%) were more likely to report depressive features, which, instead, were less frequent among doctors (compared with nurses) (OR = 0.80; 95 %CI: 0.66–0.98; I2 = 48.2 %) and HCWs who felt adequately protected (OR = 0.48; 95 %CI: 0.32–0.72; I2 = 36.3 %). Our study provided timely evidence on the correlates of depressive symptoms among HCWs during the pandemic. Early screening is crucial to develop tailored health interventions, redesigning the response to COVID-19.

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs). Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic. Results: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = –0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.

Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using ‘A MeaSurement Tool to Assess systematic Reviews’ Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the ‘Grading of Recommendations, Assessment, Development and Evaluations’ (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4–8 weeks) and tamoxifen (for response and symptoms reduction at 4–6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6–8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.

Background: Although preventive strategies have been proposed against catheter-associated urinary tract infections (CAUTIs) in intensive care units (ICUs), more efforts are needed to control the incidence rate. Aim: To distinguish patients according to their characteristics at ICU admission, and to identify clusters of patients at higher risk for CAUTIs. Methods: A two-step cluster analysis was conducted on 9656 patients from the Italian Nosocomial Infections Surveillance in Intensive Care Units project. Findings: Three clusters of patients were identified. Type of admission, patient origin and administration of antibiotics had the greatest weight on the clustering model. Cluster 1 comprised more patients with a medical type of ICU admission who came from the community. Cluster 2 comprised patients who were more likely to come from other wards/hospitals, and to report administration of antibiotics 48 h before or after ICU admission. Cluster 3 was similar to Cluster 2 but was characterized by a lower percentage of patients with administration of antibiotics 48 h before or after ICU admission. Patients in Clusters 1 and 2 had a longer duration of urinary catheterization [median 7 days, interquartile range (IQR) 12 days for Cluster 1; median 7 days, IQR 11 days for Cluster 2] than patients in Cluster 3 (median 6 days, IQR 8 days; P

Background and objectives: Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. Materials and Methods: Data for &le, 25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions&mdash, i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. Results: The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14, 95% CI: 1.08 to 4.26, p = 0.029) and being admitted for a suicide attempt (HR = 2.49, 95% CI: 1.13 to 5.49, p = 0.024) were both significant predictors of 1-year rehospitalization. Conclusions: Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients&rsquo, mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.

Background Several devices have been proposed to assess arterial stiffness in clinical daily use over the past few years, by estimating aortic pulse wave velocity (PWV) from a single measurement of brachial oscillometric blood pressure, using patented algorithms. It is uncertain if these systems are able to provide additional elements, beyond the contribution carried by age and blood pressure levels, in the definition of early vascular damage expressed by the stiffening of the arterial wall. Methods and Results The aim of our study was to compare the estimated algorithm‐based PWV values, provided by the Mobil‐O‐Graph system, with the standard noninvasive assessment of aortic PWV in patients with Marfan syndrome (ie, in subjects characterized by premature aortic stiffening and low blood pressure values). Aortic stiffness was simultaneously evaluated by carotid‐femoral PWV with a validated arterial tonometer and estimated with an arm cuff–based ambulatory blood pressure monitoring Mobil‐O‐Graph device on 103 patients with Marfan syndrome (50 men; mean± SD age, 38±15 years). Aortic PWV, estimated by the Mobil‐O‐Graph, was significantly ( P SD, 6.1±1.3 m/s) than carotid‐femoral PWV provided by arterial tonometry (mean± SD , 8.8±3.1 m/s). The average of differences between PWV values provided by the 2 methods (±1.96×SD) was −2.7±5.7 m/s. Conclusions The Mobil‐O‐Graph provides PWV values related to an ideal subject for a given age and blood pressure, but it is not able to evaluate early vascular aging expressed by high PWV in the individual patient. This is well shown in patients with Marfan syndrome.

BACKGROUND Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. METHODS Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. RESULTS The CV of PWV, measured with any of these devices, was CONCLUSIONS Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PWV.

Background. Healthcare-associated infections (HAIs) are an important issue in terms of quality of care. HAIs impact patient safety by contributing to higher rates of preventable mortality and prolonged hospita- lizations. In Italy, analysis of the currently available accreditation systems shows a substantial heteroge- neity of approaches for the prevention and surveillance of HAIs in hospitals. The aim of the present study is to develop and propose the use of a synthetic assessment tool that could be implemented homogenously throughout the nation. Methods. An analysis of nine international and of the 21 Italian regional accreditation systems was conducted in order to identify requirements and indicators implemented for HAI prevention and control. Two relevant reviews on this topic were further analyzed to identify additional evidence-based criteria. The project team evaluated all the requirements and indicators with consensus meeting methodology, then those applicable to the Italian context were grouped into a set of “focus areas”. Results. The analysis of international systems and Italian regional accreditation manuals led to the iden- ti cation respectively of 19 and 14 main requirements, with relevant heterogeneity in their application. Additional evidence-based criteria were included from the reviews analysis. From the consensus among the project team members all the standards were compared and 20 different thematic areas were identi ed, with a total of 96 requirements and indicators for preventing and monitoring HAIs. Conclusions. The study reveals a great heterogeneity in the de nition of accreditation criteria between the Italian regions. The introduction of a uniform, synthetic assessment instrument, based on the review of national and international standards, may serve as a self-assessment tool to evaluate the achievement of a minimum standards set for HAIs prevention and control in healthcare facilities. This may be used as an assessment tool by the Italian institutional accreditation system, also useful to reduce regional disparities.

UNLABELLED Hepatocellular carcinoma (HCC) is among the leading causes of cancer related death. Despite the advances in diagnosis and management of HCC the biology of this tumor remains poorly understood. Recent evidence highlighted long noncoding RNAs (lncRNAs) as crucial determinants of HCC development. In this study we report the lncRNA HOXA transcript at the distal tip (HOTTIP) as significantly up regulated in HCC specimens. The HOTTIP gene is located in physical contiguity with HOXA13 and directly controls the HOXA locus gene expression by way of interaction with the WDR5/MLL complex. HOX genes encode transcription factors regulating embryonic development and cell fate. We previously described HOX genes deregulation to be involved in hepatocarcinogenesis. Indeed we observed the marked up regulation of HOXA13 in HCC. Here by correlating clinicopathological and expression data we demonstrate that the levels of HOTTIP and HOXA13 are associated with HCC patients' clinical progression and predict disease outcome. In contrast to the majority of similar studies our data were obtained from snap frozen needle HCC biopsies (n=52) matched with their nonneoplastic counterparts collected from patients who had not yet received any HCC tailored therapeutic treatments at the time of biopsy. In addition taking advantage of gain and loss of function experiments in liver cancer derived cell lines (HuH 6 and HuH 7) we uncover a novel bidirectional regulatory loop between HOTTIP/HOXA13. CONCLUSION Our study highlights the key role of HOTTIP and HOXA13 in HCC development by associating their expression with metastasis and survival in HCC patients provides novel insights on the function of lncRNA driven hepatocarcinogenesis and paves the way for further investigation about the possible role of HOTTIP as a predictive biomarker of HCC.

OBJECTIVE: The aim of this literature review was to assess the effects of Animal-Assisted Interventions (AAI) on elderly patients with dementia or various psychiatric disorders. METHODS: We conducted a comprehensive literature search using the online PubMed network of the US National Library of Medicine & National Institutes of Health, Embase, PsycINFO, with the purpose of investigating AAI effects on cognitive functions, mood, and behaviour. RESULTS: A total of 18 articles on dementia and 5 on psychiatric disorders were included in the present review. AAI were found to have positive influences on demented patients by reducing degree of agitation and by improving degree and quality of social interaction. Few studies have assessed the effects of AAI on mood, and even fewer have assessed its consequences on cognitive functions. The results that are available indicate a positive effect on communication and coping ability, but none on cognitive performance. A substitute pet robot yielded encouraging results, but its use requires further investigation. The few studies conducted for elderly patients presenting a variety of psychiatric diagnoses produced controversial findings. CONCLUSIONS: In spite of the encouraging results of AAI, much more research examining the issue of optimal AAI duration, frequency of sessions, and suitable target group is needed.

Objective Anxiety among community-dwelling older adults has not been studied sufficiently. The aims of this cross-sectional population-based study were to estimate the point prevalence of clinically relevant anxiety symptoms and to describe their socio-demographic and clinical features, with particular focus on the association with somatic illnesses. Methods Three-hundred-sixty-six non-demented older adults (mean age 83.7±6.2, range 74–99 years) from the Faenza Project (Northern Italy) were assessed using the Cambridge Mental Disorders of the Elderly Examination-Revised (CAMDEX-R) and the Geriatric Anxiety Inventory short form (GAI-sf). Multi-adjusted regression analyses were used to estimate Odds Ratio (OR) and 95% Confidence Intervals (95% CI). Results Clinically relevant anxiety symptoms occurred in one out of five participants (point prevalence 21.0%) and were significantly associated with depression (OR 5.6 per rank; 95% CI: 3.1–10.1), physical morbidity (OR 3.5 per illness; 95% CI: 1.0–11.9) and female gender (OR 2.8; 95% CI: 1.4–5.5). Further, there were significant associations with a consumption of alcohol exceeding 1 alcoholic unit/day. Conclusions Anxiety symptoms are very common in older subjects, especially when medically ill. Depression and alcohol consumption often co-occur with late-life anxiety symptoms, thus requiring special attention in daily clinical practice.

The aim of this cross-sectional study is to investigate mild cognitive impairment (MCI) using the Mini-Mental State Examination in an Italian cohort (N = 6921; mean age 71.6 ± 7.5; 59.2% women). First, we applied psychometrically derived criteria for MCI regardless of presence/absence of subjective cognitive complaints (SCC); second, we implemented the analyses only on the SCC subsample. The estimated MCI prevalence was 6.0%. Amnestic- and non-amnestic MCI single domains accounted for 4.3% and 13.5% of the cases, respectively. Amnestic- and non-amnestic MCI multiple domains occurred in 2.0% and 4.5% of the cases, respectively. The 33.8% of the SCC subsample (6.0% of the cohort) had MCI. Stroke, diabetes and depressive symptoms were commonly associated to MCI suggesting that this common condition is associated with many correlates in Italian older persons. It deserves attention since it is early detectable and potentially preventable.

The pathophysiology of Alzheimer's disease (AD) is influenced by sorting-protein related receptor (sorLa) that is less expressed in AD patients. The gene encoding sorLa (SORL1) has been investigated as a susceptibility factor for late-onset AD (LOAD) with conflicting results. Our objectives were to confirm the association between SORL1 SNPs and LOAD in two independent South-European centers and to perform a mega-analysis of published samples. We analyzed three SORL1 SNPs (intron 6: rs668387; rs689021; rs641120) from the Greece-Italy Genetic Association Study on lateonset AD (GIGAS_LOAD). Greek sample included 96 patients with LOAD (DSM-IV) and 120 unrelated controls. In Italy, a community-based sample is ongoing. 47 LOAD patients and 165 controls were recruited until study endpoint. These samples and previously published ones (Alzgene) were pooled as in a single study. A test for trend was used to analyze genotype association. In the GIGAS_LOAD sample no association was detected between SORL1 genotypes and LOAD. Conversely all SNPs were associated with LOAD in mega-analysis based on ordinal classification of genotypes (Armitage's test: p < 0.001). Although our analysis of pooled samples has positive results for the association between SORL1 and AD, there is substantial heterogeneity across studies. Thus further examination into SORL1 SNPs and the population is necessary to determine the role of SORL1 in LOAD.

OBJECTIVE: The aim of this study was to evaluate the association between vision and hearing impairment and depressive-anxiety syndrome in a large population participating in the Faenza Project, Northern Italy. METHOD: The study population consisted of 7389 participants not affected by dementia, 4408 (59.7%), of whom were women, mean age ± standard deviation (±SD) 71.9 (±7.7) years. Information about previous or current psychiatric symptoms, including sleeping and eating habits, non-verbal language and ability in activity of daily living was used to investigate depressive and anxiety syndrome. A semi-structured interview was administered to survey the presence of sensory impairment. Logistic regression analyses were used to evaluate the association between sensory impairment and depressive-anxiety syndrome estimating Odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The prevalence of vision and hearing impairment was 1.4% and 0.2%, respectively, with an increasing trend in people aged 75+ years (p < 0.001). The prevalence of depressive syndrome was higher among vision-impaired participants (20.2% vs. 9.3%, p < 0.001), especially women (22.9%) and persons aged 75+ years (22.1%). The prevalence of anxiety syndrome was higher in the hearing-impaired group (25.0% vs. 11.0%, p = 0.09). Vision-impaired participants, especially women and participants aged 75+ years had have a twofold higher probability to have depressive syndrome (OR = 2.03, 95% CI = 1.21-3.38), and hearing-impaired individuals showed an increased probability of presenting anxiety syndrome (OR = 2.71, 95% CI = 0.86-8.55), although these results were not statistically significant. CONCLUSION: This study's findings suggest that sensory impairment in older adults can increase their probability of experiencing depressive and anxiety syndrome. Correction of these deficits could improve the quality of life in this population.

OBJECTIVE: The objective of this study was to assess whether a minimally invasive protocol can be effective in the long-term control of necrotic areas and pain in patients suffering osteonecrosis of the jaw associated with the use of bisphosphonate drugs (BRONJ). STUDY DESIGN: Thirty-four consecutive patients (14 male, 20 female) with BRONJ under treatment with zoledronate, pamidronate, or alendronate were enrolled. All of the patients received professional oral hygiene treatment and antiseptic oral rinses, and if in pain they assumed an antibiotic therapy with amoxicillin/clavulanate potassium and metronidazole for ten days. At the baseline visit, as well as at each 3-month recall, the size of the osteonecrotic lesions were measured and the pain level assessed with a visual analog scale. RESULTS: The results from the general linear model showed a statistically significant (F = 16.1; P < .01; r(2) = 0.95) time-related decrease in the size of exposed bone areas during the nonsurgical therapy (from 12.5 ± 12.0 mm to 8.8 ± 10.3 mm). CONCLUSIONS: This conservative protocol seems to provide successful treatment in the vast majority of patients.

BACKGROUND: To evaluate the effects of pet therapy on cognitive function, mood and perceived quality of life on elderly inpatients (mean age 84.7 years; 95.2% women) affected by dementia, depression and psychosis. METHODS: Mini-Mental State Examination (MMSE) and 15-items Geriatric Depression Scale (GDS) were administered to 10 patients (pet group) and 11 controls (control group) together with a self-perceived quality-of-life questionnaire, before and after a pet therapy intervention that lasted 6 weeks. MMSE and GDS mean scores were compared between and within groups by Student's t-test. RESULTS: Both the pet group and control group improved on GDS and MMSE. Within the pet group, GDS symptoms decreased by 50% (from 5.9 to 2.7, P= 0.013), whereas mean MMSE score increased by 4.5 (P= 0.060). The between group comparison showed a positive effect of pet therapy intervention on GDS (P= 0.070). Most of the participants reported an improvement of their perceived quality of life. CONCLUSIONS: Pet therapy is efficient in improving depressive symptoms and cognitive function in residents of long-term care facilities with mental illness.

Background: Homocysteinemia (Hcy) increase and risk factors in HIV-positive patients are not clear yet. Methods: HIV-positive patients on stable highly active antiretroviral therapy (HAART) regimens for at least 6 months were enrolled in this cross-sectional study. Among other factors, vitamin B12, folate and length of exposure to protease inhibitors (PIs) were evaluated for their possible correlation with hyper-Hcy (>13 µmol/l in females; >15 µmol/l in males) by logistic regression analysis. Results: Ninety-eight HIV-positive patients were recruited. Twenty-eight (28.6%) had hyper-Hcy. Length of exposure to antiretroviral therapy and PIs did not result to be significantly associated with hyper-Hcy risk. Normal folate level was the only factor associated with the outcome, resulting protective from hyper-Hcy, either at univariate (OR = 0.22; CI 95% = 0.06–0.86; p = 0.029) and multivariable (OR = 0.24; CI 95% = 0.06–0.94; p = 0.04) logistic regression analysis. Folate predictive value of hyper-Hcy risk was driven by levels in the lowest quartiles of the study population (i.e. Conclusions: No significant correlations were observed between hyper-Hcy and length of exposure to antiretroviral therapy or PIs. Folate could be a confounding factor in the association between hyper-Hcy and PI exposure found by others. The potential value of folate supplementation, in those who are deficient and in those with hyper-Hcy, merits study.

Background. It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy. Methods. In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (C trough ) values were determined at weeks 1, 4, 12, and 24 of the study. Results. Among 230 patients, virological benefit (defined by an HIV RNA load of

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure.Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models.Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values.Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

Human herpesvirus oesophagitis in human immunodeficiency virus positive patients is caused by cytomegalovirus and herpes simplex virus; no cases of oesophagitis and oesophagobrochial fistula as a result of varicella zoster virus (VZV) have been reported to date. This report describes the case of a patient with a 2–3 mm deep oesophageal ulcer whose viral culture was positive for VZV. The patient was treated with acyclovir with resolution of the symptomatology. After the end of the induction treatment, because of the onset of fever and fits of coughing during eating, the patient underwent oesophagography, which showed an ulcer with an oesophagobronchial fistula in the middle and lower third of the oesophagus. This case report stresses the role of VZV infection as a possible cause of oesophagobronchial fistula, a rare but benign condition in patients with AIDS.