BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.

BACKGROUND: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. MATERIALS AND METHODS: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines. RESULTS: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. CONCLUSIONS: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients.

Quality of life, Stress, and Burnout of Italian nurses during the outbreak of COVID-19: a cross-sectional study / La qualità della vita, stress e burnout negli infermieri durante il periodo della Pandemia da Covid-19 in Italia: uno studio trasversale.

INTRODUCTION: The COVID-19 pandemic was a whispered problem for nurses, causing feelings of anxiety, stress, and burnout. Many studies investigated the pandemic's negative effects on nurses, but the relationship between burnout and the quality of life (QoL) in Italian nurses was lacking. AIM: To describe Italian nurses quality of life and stress during the Covid-19 outbreak. METHODS: METHODS: We conducted a cross-sectional study between March 25, 2020, to May 15, 2020. The MBI scale was used to detect burnout, while the SVQI was for nurses' quality of life (QoL). We used descriptive and correlational statistical tests between the scales and risk factors. The significance level was set at P. 0.05. RESULTS: A total of 384 nurses were assessed, 58.1% (223) were female, 41.9% (161) were male. Depersonalization appeared in 85% of cases, emotional exhaustion in 52.3%, and personal accomplishment in 17.4%. Overall, nurses report a dissatisfaction with the physical, emotional and social QoL. The factors that contribute to onset of the syndrome was: gender (p = 0.003), ward (p = 0.03), care to COVID-19 patients (p = 0.02). Women are dissatisfied with physical (p = 0.001), emotional (p = 0.001) and social (p =0.002) QoL. Statistically significant differences by department (p = 0.01) and geographical area of Northern Italy (p = 0.02). CONCLUSION: During the COVID-19 outbreak, some factors studied are associated with high-stress levels and low physical and social QoL. Women were the gender most affected by the effects of the pandemic.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

Ethyl Glucuronide and Ethyl Sulphate in Urine: Caution in their use as markers of recent alcohol use.

AIM: To clarify the role of the ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), in monitoring alcohol consumption. METHOD: We recruited 7 female and 17 male volunteers who were instructed to consume a quantity of beer (containing 48 gm ethanol) with food in one session. We examined urinary excretion of EtG and EtS over time and looked for correlations between the concentrations of the metabolites EtG and EtS. RESULTS: EtG concentrations in urine varied between 0.026 and 430.372 µg/ml with average values between 11.85 µg/ml (SD 19.75), 30 min after alcohol intake, and 100.39 µg/ml (SD 101.34), 4.5 h after alcohol intake. EtS urinary concentration ranged from 0.006 to 101.432 µg/ml with average values between 4.77 µg/ml (SD 5.42), 30 min after alcohol intake, and 30.14 µg/ml (SD 27.20), 4.5 h after alcohol intake. Spearman's test showed that urinary EtG and EtS correlated significantly at several time points. CONCLUSION: The great interindividual variability in their excretion suggests caution in the use of urinary measurement of these metabolites in forensic investigations.

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab.

Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1.Methods: Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated.Results: 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI: 0.17-0.57), p < .001). Median PFS was 2.6 months (95% CI: 1.9-5.1) among patients with PS2 and 11.3 months (95% CI: 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI: 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. PS 2 remained predictive of poor outcomes in multivariate analysis.Conclusion: PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.

[Emergency nurses and workplace violence: a cross-sectional study in Campania, South Italy]. / Gli infermieri di pronto soccorso e la violenza sul luogo di lavoro: un'indagine trasversale nel contesto campano.

AIM: To determine the characteristics of workplace violence towards emergency nurses in Campania, South Italy. INTRODUCTION: In Italy, workplace violence is a severe and widespread problem. A national survey describes that, working in South Italy significantly increases the probability of being exposed. However, available data in Campania workplace violence towards nurse emergency department (ED) is lacking. METHOD: We used a cross-sectional design, in two emergency department. Between April and May 2019, we distributed a questionnaire (QIN16VIPs). Three types of violence have been investigated: verbal/physical violence, verbal violence and physical violence. The data were analyzed using procedures of descriptive statistics. RESULTS: A total of 83 questionnaires (response rate 92.3%), 48.2% of emergency nurses experienced verbal violence, 21.7% both verbal and physical violence and only 28.9% denied having experienced either. Nurses feeling at risk in emergency setting were more exposed to workplace violence (p=0.001). Anxiety (p=0.023) and anger (p=0.001) were perceived feeling with significant repercussions on the degree of evidence working in ED (p=0.043) and on trust in management (p=0.001). CONCLUSIONS: Workplace violence turns out to be a serious and widespread problem that generates negative feelings in the attacked subject that affect the personal and work dimension. The promotion of simple and anonymous reporting systems would help nurses to be more aware of the importance of reporting the event, which is still in deficit today, thus preventing a true and proper estimate of the phenomenon. Future research should be focused for preventive measures could be drawn up to reduce the problem.

Long-Term Risk of Stroke After Transient Global Amnesia in Two Prospective Cohorts.

Background and Purpose- Transient global amnesia (TGA) is known as a benign syndrome, but recent data from neuroradiological studies support an ischemic cause in some cases, which might suggest an increased susceptibility to cerebrovascular events. We determined the long-term risk of stroke after a first TGA in 2 independent prospective cohorts. Methods- In 2 independent prospective cohorts of patients with TGA (OXVASC [Oxford Vascular Study], population-based; NU (Northern Umbria) cohort, TGA registry), cardiovascular risk factors and long-term outcomes, including stroke and major cardiovascular events, were identified on follow-up. Cardiovascular risk factors were treated according to primary prevention guidelines. In OXVASC, the age-/sex-adjusted risk of stroke during follow-up was compared with that expected from the rate in the underlying study population. Results- Among 525 patients with TGA (425 NU and 100 OXVASC), mean (SD) age was 65.1 (9.5) years and 42.5% male. Hypertension (58.1%), dyslipidemia (40.4%), and smoking (36.4%) were the most frequent cardiovascular risk factors. The risk of stroke was similar in the 2 cohorts, with a pooled annual risk of 0.6% (95% CI, 0.4-0.9) and a 5-year cumulative risk of 2.7% (1.1-4.3). Moreover, the stroke risk in OXVASC cases was no greater than that expected in the underlying study population (adjusted relative risk=0.73; 0.12-4.54; P=0.74). Conclusions- TGA does not carry an increased risk of stroke, at least when cardiovascular risk factors are treated according to primary prevention guidelines.

Stage-related outcome for thymic epithelial tumours.

BACKGROUND: Thymic epithelial tumours (TETs) are characterized by a wide variety of biological behaviors. Radical resection and stage are strong prognostic factors. Aim of this study is to review our Single Center Experience. METHODS: One hundred and seventy-seven patients observed in the period from January 2000 to December 2016 were included in the study. Data regarding clinicopathologic features, treatment, and survival were collected. Stage-related clinical standpoints and therapeutic options were also evaluated. RESULTS: Non-surgical treatment was primarily performed in 15 (8.47%), unresectable disease was intraoperatively found in 12 cases (7.4%). The analysis of 150 patients undergoing curative surgery revealed 70 stage I TET (46.66%), 49 stage II (32.66%), 19 stage III (12.66%), 6 stage IVa (4%) and 6 stage IVb (4%) at the first hospital admission. Histology identified 12 A thymoma (8%), 38 AB (25.33%), 24 B1 (16%), 50 B2 (33.33%), 19 B3 (12.66%) and 7 carcinomas (4.66%). The mean follow up time was 84.14 months (sd = 61.68 months). Disease relapse occurred in 13 patients (8.78%) at a mean period of 78.85 months (sd = 60.87 months) after surgery. Exitus due to thymoma happened in 6 cases (4.05%) after a mean survival of 56.02 months (sd = 25.17 months). The 5-year overall survival rate was 0.94 (95%CI 0.88-0.97) and the 5-year disease-free survival rate was 0.90 (95%CI 0.83-0.94). The 5-year overall survival rates were 96.1% (95% CI, 89.9-98.5%) for the early stages and 87.4% (95% CI, 65.6-95.8%) for the advanced stages (p = 0.670). The 5-year disease-free survival rates resulted being 98.8% (95% CI, 92.3-99.8%) for the early stages and 59.8% (95% CI, 37.8-76.2%) for the advanced stages (p < 0.001). CONCLUSIONS: Advanced stage TETs are characterized by higher mortality and recurrence rates. Although technically demanding, surgery, as part of multimodality therapy, could prolong survival. Iterative surgical treatment of recurrences is a viable option for selected patients. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Perugia and Terni University Hospitals [Code T1003] and was retrospectively registered.

Significance of Morphine Concentration in Bile, Liver, and Blood: Analysis of 52 Cases of Heroin Overdoses.

Forensic pathologists are requested to select matrices alternative to blood in cases of toxicological interest in which blood is not available for different reasons. We evaluated morphine concentrations in blood, bile, and liver samples in 52 cases of heroin overdoses, relating them to each other, to understand the information that could be derived from their analysis. Gas chromatography/mass spectrometry analysis was performed for all the samples positive on screening for opiates. Shapiro-Wilk test, nonparametric Mann-Whitney test, linear regression analysis, and Bland-Altman test were used for analysis. Linear regression demonstrated that there was not a statistically significant association in morphine concentrations between blood and bile and blood and liver. Mean liver/blood ratio was 2.76, varying from 0.131 to 13.379, and bile/blood ratio was 28.79, varying from 0.28 to 559.16. According to these results, bile analysis is a "screening test"; biliary or hepatic concentration of morphine cannot provide information on hematic concentration at the time of death, having no forensic value taken individually.

Violence towards Emergency Nurses: The 2016 Italian National Survey-A cross-sectional study.

AIM: To analyse the dimensions and characteristics of violence towards Emergency nurses in a national context (Italy). BACKGROUND: Nurses are the most exposed to workplace violence, especially in Emergency Department contexts. METHODS: A cross-sectional study was conducted in all Italian regions. Descriptive analyses were used to examine violence from patients and relatives (Type II violence) concerning personal characteristics of the Emergency nurses and perpetrators, environmental and organisational factors. Multinomial logistic regression analysis was used to investigate risk factors. RESULTS: About 76.0% of Emergency nurses experienced verbal violence, 15.5% both verbal and physical violence and only 8.5% denied having experienced either. Older age and more experience in Emergency settings are protective factors. Working in the South of Italy significantly increases the probability of being exposed. DISCUSSION: There are many factors explaining violence, but some correlations are not clear. CONCLUSION: Factors that have a positive effect on this problem include: specific training for younger nurses, a strong alliance between users and health personnel to restore a relationship of trust between parties, physical barriers and appropriate architectural measures. IMPLICATIONS FOR NURSING MANAGEMENT: Comprehensive approaches can represent an effective strategy to counteract workplace violence.

Cuff pressure monitoring by manual palpation in intubated patients: How accurate is it? A manikin simulation study.

BACKGROUND: Endotracheal intubation (ETI) for mechanical ventilation has a central role in the Intensive Care Unit (ICU). ETI is one of the main risk factors for the development of ventilator-associated pneumonia (VAP) as its presence reduces the natural defences of the upper airway and allows the micro-suction of secretions in the airways. In order to minimise such complications, it is fundamental to maintain a suitable pressure inside the tube cuff. AIM AND SCOPE: The main objective of the present study is to evaluate the effectiveness and reliability of palpation method, performed with the operators fingers, for detecting the tube cuff pressure. RESULTS: The study was performed using a manikin to test the pressure of the ETT cuff, on a sample constituted by nurses employed in three Italian ICU from two different Umbrian hospitals. From a total of 68 participants, detection by palpation method revealed to be not correct in 68% of cases; in particular, only 10% of respondents can correctly detect a pressure in the recommended range (20-30cmH2O) using palpation. Moreover it was possible to highlight that the participation in emergency courses has a positive effect on the correct measurement of cuff pressure using the palpation method (V=0.501). CONCLUSIONS: The study, in agreement with the literature, confirms the thesis that the palpation method is inadequate to determine an estimate of the pressure existing inside the cuff.

How Teaching and Internship Influence the Evidence-Based Practice Approach of Nursing Students: A Longitudinal Study.

AIM: The study aimed to analyze students' approach to evidence-based practice and evaluate the effect of teaching (based on lessons in statistics, epidemiology, evidence-based nursing, bioengineering, English language) and internship experiences on the attitude of nursing students to evidence-based practice. METHOD: In 2019,one hundred nineteen second-year nursing students from an Italian university were involved in a pre-post longitudinal study. The Italian version of the Student-Evidence Based Practice Questionnaire was administered to nursing student in four moments of one academic year. RESULTS: The Student-Evidence Based Practice Questionnaire showed different mean scores based on the four moments of the survey with a significant increase after the experience of planning clinical cases with an online simulation system. In particular, the aptitude subscale does not have significant improvements in the various phases of the study. Conversely, the support of the clinical tutor affects student performance. The didactic module on evidence-based nursing develops the ability to assess the quality of the information found and its sharing. Basic English proficiency is not significantly correlated. CONCLUSION: To develop evidence-based practice knowledge, aptitude, and skills in nursing students, it is necessary to strengthen the learning opportunities both in classroom lessons and in simulation and internship experiences.

Long-Term Impacts of the COVID-19 Pandemic on Drug/Alcohol Use Prevalence in a Population with Substance Use Disorders.

As time passes, the long-term effects of the COVID-19 pandemic are becoming increasingly apparent. The extreme restrictions imposed during the pandemic have had detrimental impacts on the most vulnerable groups, such as individuals suffering from substance and/or alcohol disorders (SUDs). This study reports quarterly laboratory data on alcohol and drug use in 150 subjects with SUDs that were examined using hair analysis for 2 years before the start of pandemic until after the end of the Italian health emergency. Overall, it was found that the number of subjects who used heroin, cocaine, and MDMA all decreased during the 2020 and 2021 lockdowns, increasing during reopening and subsequently stabilizing close to pre-COVID levels. Cannabis use was less impacted, remaining stable throughout the pandemic. Alcohol and benzodiazepine use both increased significantly during the lockdowns, displaying an opposing trend. While benzodiazepine use progressively returned to baseline levels, alcohol remained at significantly increased levels, even in September 2022. Long-term heavy drinking combined with substance use should be seriously considered, since these results in several health and social problems alongside alcohol-related comorbidities. Thus, appropriate response plans should be implemented both during and after the pandemic, whilst focusing on those who are most vulnerable.

Socio-Economic Factors Associated with Ethnic Disparities in SARS-CoV-2 Infection and Hospitalization.

BACKGROUND: There is evidence that non-Italians presented higher incidence of infection and worse health outcomes if compared to native populations in the COVID-19 pandemic. The aim of the study was to compare Italian- and non-Italian-born health outcomes, accounting for socio-economic levels. METHODS: We analyzed data relative to 906,463 people in Umbria (Italy) from 21 February 2020 to 31 May 2021. We considered the National Deprivation Index, the Urban-Rural Municipalities Index and the Human Development Index (HDI) of the country of birth. We used a multilevel logistic regression model to explore the influence of these factors on SARS-CoV-2 infection and hospitalization rates. Diagnosis in the 48 h preceding admission was an indicator of late diagnosis among hospitalized cases. RESULTS: Overall, 54,448 persons tested positive (6%), and 9.7% of them were hospitalized. The risk of hospital admission was higher among non-Italians and was inversely related to the HDI of the country of birth. A diagnosis within 48 h before hospitalization was more frequent among non-Italians and correlated to the HDI level. CONCLUSIONS: COVID-19 had unequal health outcomes among the population in Umbria. Reduced access to primary care services in the non-Italian group could explain our findings. Policies on immigrants' access to primary healthcare need to be improved.

Optimizing the risk stratification of astrocytic tumors by applying the cIMPACT-NOW Update 3 signature: real-word single center experience.

Our work reports implementation of a useful genetic diagnosis for the clinical managment of patients with astrocytic tumors. We investigated 313 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. The cIMPACT-NOW Update 3 (cIMPACT-NOW 3) markers, i.e., alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 96.4% of IDHwt cases. Interestingly, it was also found in 48,5% of IDHmut cases. According to the genomic profile, four genetic subgroups could be distinguished: (1) IDwt/cIMPACT-NOW 3 (n = 270); (2) IDHwt/cIMPACT-NOW 3 negative (= 10); (3) IDHmut/cIMPACT-NOW 3 (n = 16); and 4) IDHmut/cIMPACT-NOW 3 negative (n = 17). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDHwt, HR 2.91 95% CI 1.39-6.06), and validated the prognostic value of the cIMPACT-NOW 3 signature (cIMPACT-NOW 3, HR 2.15 95% CI 1.15-4.03). To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.

A New Medium (HistoCold) for Surgical Specimens Preserving to Improve the Preanalytic Issues in Histopathological Samples Handling: Morphologic and Antigenic Analysis.

Introduction: The onset of precision medicine has led to the integration of traditional morphologic tissues evaluation with biochemical and molecular data for a more appropriate pathological diagnosis. The preanalytic phase and, particularly, timing of cold ischemia are crucial to guarantee high-quality biorepositories of formalin-fixed paraffin-embedded (FFPE) tissues for patients' needs and scientific research. However, delayed fixation using the gold-standard and carcinogenic fixative neutral-buffered formalin (NBF) can be a significant limitation to diagnosis and biopathological characterization. HistoCold (patented; Bio-Optica Milano S.p.A., Milano, Italy) is a nontoxic, stable, and refrigerated preservative solution for tissue handling. This study examined HistoCold's potential role in improving the preanalytic phase of the pathological diagnostic process. Materials and Methods: Breast, lung, or colorectal cancers (20, 25, and 10 cases, respectively) that were to be surgically resected were recruited between 2019 and 2021. Once specimens were surgically removed, three residual samples for each patient were first promptly immersed into HistoCold for 24, 48, and 72 hours and then FFPE. These were compared with routine specimens regarding morphologic features (hematoxylin and eosin) and tissue antigenicity (immunohistochemical stains). Results: Good concordance regarding both the morphologic characteristics of the neoplasms and their proteins expression between the routine and HistoCold handled tissues were found. The tissue handling with the solution never affected the histopathological diagnosis. Conclusions: The use of HistoCold for samples transporting is easy, allows for improving the management of cold ischemia time, and monitoring the fixation times in NBF, resulting in good quality tissue blocks for biobanking. Moreover, it could be a candidate to eliminate formalin from operating theaters. HistoCold looks very promising for the preanalytic phase of human tissues handling in the era of precision medicine, to provide the best service to patients, and to scientific research.

The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

Patients who leave the Emergency Department without being seen. Has COVID-19 affected this phenomenon?

BACKGROUND AND AIM: Patients who present to an Emergency Department (ED) and leave without being seen by a physician represent a safety concern because they may become severely ill and experience adverse events as a result of lacking or delayed ED treatment. Prior to the COVID-19 outbreak, the increasing number of patients accessing care through the ED in Italy and throughout the world has had implications for health policies. METHODS: A retrospective cohort study that included all ED visits from 1st January 2013 to 31st December 2018 in the Perugia University Hospital has been carried out. RESULTS: During the 5 years investigated 26,344 out of 300,372 (8.77%) patients who attended the ED left the triage area before being seen with an average of 439 patients per month. The same phenomenon has been analysed from February to October 2020. During these 9 months there were a total of 1,824 out of 30,990 (5.88%) patients who left the ED without being seen with an average of 202 per month. The latter value is one third lower than the one related to the period investigated prior to the COVID-19 outbreak. CONCLUSIONS: Such investigation could help to differentiate actual essential demand from non-essential demand within the ED, which could inform quality-improvement policies. Several strategies could be implemented to lower the proportion of patients who leave the department without being seen. Reorganising the activities in the ED with different paths should be implemented with the aim of reducing waiting times and in turn patients' satisfaction.

Patterns of Prescription Medicine, Illicit Drugs, and Alcohol Misuse among High-Risk Population: A Factor Analysis to Delineate Profiles of Polydrug Users.

Polydrug use is a serious health and social problem worldwide. Treatment remains a challenge because it requires planning based on estimates of the nature and extent of drug consumption and the characteristics of the population in need. To this end, 103 subjects, who voluntarily asked to begin rehabilitation treatment, were monitored through hair analysis to investigate the nature and extent of their polydrug use. A factor analysis was carried out to delineate polydrug user profiles based on the following variables: age, sex, type of illicit drug use, type of prescription drug misuse, and amount of alcohol consumption. Twenty-three percent of subjects tested positive to more than one illicit drug (mainly cocaine), 44% to unprescribed drugs (mainly benzodiazepines), and 66% were hard drinkers. The profiles of drug users outlined included "single drug cocaine user", and "single drug opiate user". Moreover, a particularly problematic profile of cocaine users, common between genders and age groups, who combine high levels of alcohol and unprescribed benzodiazepines and opiates, emerged ("hard polydrug abusers"). From a treatment policy perspective, these findings support the importance of preventive analysis before rehabilitation treatment begins in order to identify different patterns of drug abusers to implement personalized multidisciplinary measures.