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To investigate the dynamic evolution of vaccine hesitancy toward both COVID-19 and influenza in a context characterized by the compresence of SARS-CoV-2 pandemic and seasonal flu epidemics, a two times repeated cross-sectional exploratory design was performed at Udine Hospital (Italy) following a cohort of 479 adult patients with a previous history of SARS-CoV-2 infection in 2020. Vaccine attitude was assessed through standardized telephone interviews performed at 12 and 18 months after the acute illness. The first interview reported the success of the 2020/21 seasonal influenza immunization with 46.8% (224/479) of the participants showing a positive attitude, especially the elderly and people with comorbidities ( p  < .001), but the investigation conducted at 18 months showed a drastic drop in flu shot acceptance (30/166, 18.1%). On the other hand, a great increase in vaccinations against SARS-CoV-2 occurred after the introduction of Green Pass (26.7% vs 72.9%). The major drivers of flu vaccine skepticism were represented by the feeling of protection regardless of prevention and by concerns regarding vaccines safety and efficacy; conversely compulsory strategies seemed to play a secondary role, since only a minority of the participants identified in the restrictions induced by the certification the major incentive to get immunized against SARS-CoV-2. The focus on this peculiar historical period helps to take a step forward in the comprehension of the complexity and dynamicity of the vaccine hesitancy phenomenon. Future vaccination campaigns will need to consider the role of personal opinions and emotions, interpreted according to the social and political context.

Background: Patients undergoing Extracorporeal Membrane Oxygenation (ECMO) are particularly susceptible to infections: 42% experience sepsis and 26% develop a nosocomial infection (NI). Whether antibiotic prophylaxis is effective in reducing mortality and its effects on the rate of NIs is currently unclear., Research Question: Can antibiotic prophylaxis decrease 30-day mortality for patients on ECMO? Can antibiotic prophylaxis prevent the occurrence of NIs in these patients?, Study Design and Methods: A systematic review and meta-analysis was conducted. We searched PubMed, Scopus, and CINAHL libraries from inception to June 12, 2024. Two researchers were involved in abstract screening and three researchers were involved in full text selection., Results: A pooled population of 7,996 patients is represented by 5 retrospective studies. Reported mortality ranges between 46 and 58% and the NIs rate is between 14 and 62%. Regarding 30-day mortality, the random-effects model (I 2  = 65%) indicates a non-statistically significant difference between the antibiotic prophylaxis group and the non-prophylaxis group (OR 0.76; 95%CI 0.37-1.59). For the NIs rate, a fixed-effect model (I 2  = 36%) shows an OR of 0.81 (95%CI 0.71-0.92) in favor of the antibiotic prophylaxis group, with a number-needed-to-treat (NNT) of 39.7 patients., Conclusion: According to a very low degree of certainty, antibiotic prophylaxis appears to have no impact on the 30-day mortality rate of ECMO recipients. The risk of NIs seems to decrease with antibiotic prophylaxis, even though the NNT is high. Prospective high-quality studies that address these specific clinical questions are necessary., Clinical Trial Registration: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024567037., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: The Alzheimer's Prevention Initiative (API) Generation Studies evaluated the BACE inhibitor umibecestat for Alzheimer's disease (AD) prevention. The studies were terminated early, and the reversibility of umibecestat's side effects was assessed., Methods: Cognitively unimpaired 60- to 75-year-old apolipoprotein E (APOE) ε4 homozygotes and heterozygotes (the latter with elevated brain amyloid deposition) (n = 1556) received umibecestat (50 or 15 mg daily) or placebo for 7 months on average and were followed for a median (interquartile range) of 4 (3 to 6) months after washout., Results: Compared to placebo, umibecestat-treated participants had small, non-progressive, but statistically significant decline in performance on certain cognitive batteries including Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and API Preclinical Composite Cognitive test, but not Clinical Dementia Rating-Sum of Boxes. RBANS differences were no longer significant at the end of follow-up., Discussion: In people at genetic risk for AD, high-dose beta-site amyloid precursor protein cleaving enzyme (BACE) inhibition was associated with early mild cognitive worsening, which reversed shortly after washout, suggesting a symptomatic side effect not associated with neurodegeneration. Fully anonymized data, images, and samples are available upon request for further research on BACE inhibition., Highlights: This is the first trial with blinded assessment of reversibility of BACE inhibitor side effects. Umibecestat was tested in cognitively unimpaired persons at genetic risk for AD. Umibecestat led to early mild cognitive decline that reversed shortly after washout. This suggests a potentially manageable effect not associated with neurodegeneration. Further research may determine the future of BACE inhibition in AD prevention., (© 2024 Novartis Pharma AG. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Renal and genitourinary ultrasound are fundamental resources employed by emergency and critical care healthcare providers to make prompt diagnoses and perform ultrasound-guided procedures. At the bedside, ultrasound can aid in the diagnosis of relevant pathologies, such as post-renal obstruction or kidney stones, and life-threatening conditions such as aortic dissection or hemoperitoneum. A narrative overview was performed, providing an updated review of renal and genitourinary ultrasound for emergency and critical care healthcare providers, emphasizing its advantages and the latest advances in the field. A thorough summary that can be utilized as a guide for emergency and critical care healthcare providers is presented. The daily hemodynamic management of critically ill patients involves the implementation of new protocols, such as VexUS or the evaluation of the renal resistance index. The role of ultrasound in managing acute nephropathy and genitourinary issues is increasingly crucial given its bedside availability, thus this imaging modality not only facilitates the initiation of therapeutic interventions but also provides swift prognostic insights that are vital to provide tailored patient care. As further advances in ultrasound will arise, it is important for healthcare providers to foster the use of these technologies capable of improving patient outcomes.

Background: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events., Methods: A systematic review and meta-analysis was performed., Results: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I 2  = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I 2  = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I 2  = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I 2  = 0%)., Conclusion: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events., Clinical Trial Registration: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768., (© 2024. The Author(s).)

Objectives: To describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients., Methods: A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response., Results: Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9-27.8) months. Seroreversion was 98.5% (95% CI: 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99-0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97-0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39-0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37-0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57-0.98, p 0.038; HR: 1.77, 95% CI: 1.19-2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014)., Discussion: First-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the prevalence of neuropsychiatric symptoms 2 years after the COVID-19 acute phase and to identify biobehavioral risk factors., Methods: This 2-year prospective study assessed adult individuals with COVID-19 via face-to-face interview and laboratory testing at onset, and via telephone interview at 2-year follow-up. Data collected included COVID-19 severity and management at onset, as well as depression, anxiety, insomnia, cognitive failure, and fatigue at follow-up using standardized assessment tools., Results: Out of 1,067 screened COVID-19 patients, 230 completed the 2-year follow-up (female, 53.5%; aged>40, 80.9%; native Italian, 94.9%; medical comorbidity, 53.5%; chronic medication, 46.3%; moderate to severe COVID-19, 24.9%; hospital admission, 28.7%; ICU, 5.2%). At follow-up, 9.1% had anxiety, 11.3% depression, 9.1% insomnia, 18.3% cognitive failure, and 39.1% fatigue, of clinical relevance. Headache (OR = 2.49, 95% CI = 1.01-6.16, p = 0.048), dyspnea (OR = 2.55, 95% CI = 1.03-6.31, p = 0.043), and number of symptoms (OR = 1.23, 95% CI = 1.01-1.51, p = 0.047) at onset were associated with anxiety at follow-up; dyspnea at onset was associated with depression at follow-up (OR = 2.80, 95% CI = 1.22-6.41, p = 0.015); number of comorbidities at onset was associated with insomnia at follow-up (OR = 1.48, 95% CI = 1.06-2.08, p = 0.022); female gender (OR = 2.39, 95% CI = 1.14-5.00, p = 0.020) and number of symptoms (OR = 1.20, 95% CI = 1.02-1.42, p = 0.026) at onset was associated with cognitive failure at follow-up; number of comorbidities (OR = 1.33, 95% CI = 1.03-1.73, p = 0.029) and symptoms (OR = 1.19, 95% CI = 1.04-1.37, p = 0.013) and raised interleukin 6 levels ( OR = 4.02, 95% CI = 1.42-11.36, p = 0.009) at onset was associated with fatigue at follow-up., Conclusions: COVID-19 survivors, especially if female, with preexisting health problems, and with a more severe acute phase, may present with long-lasting neuropsychiatric sequalae, urging interventions to sustain recovery particularly in these higher risk individuals.

. Care assistants at the international level: a narrative review., Introduction: At the international level, the role of care assistants, their competencies and scope of their professional practice has been debated for many years. Periodically updating the state of the art regarding the different training pathways, expected competencies, and responsibilities of care assistants at the international level is crucial for monitoring the evolution of these professional profiles., Objective: To map the available classifications of care assistants at the international level, by describing (a) where these figures receive training, with which pathways, and for which competencies, and (b) where they can work and with what level of professional autonomy/interdependence with respect to other healthcare professions., Method: A narrative review of the literature was conducted by examining documents produced by the World Health Organization and the European Union; and that of three reference countries, the United Kingdom, Canada, and the United States of America., Results: Fourteen documents were selected. Numerous care assistant profiles are described in available classifications, totaling 32 different profiles; these individuals may receive training in upper secondary school or colleges to perform a range of competencies. They may be supervised in their practice not only by nurses. In some countries, compulsory registration is required., Discussion: The results show an important heterogeneity in care assistant figures internationally.

Digitization has become involved in every aspect of life, including the healthcare sector with its healthcare professionals (HCPs), citizens (patients and their families), and services. This complex process is supported by policies: however, to date, no policy analysis on healthcare digitalization has been conducted in European countries to identify the main goals of digital transformation and its practical implementation. This research aimed to describe and compare the digital health policies across four European countries; namely, their priorities, their implementation in practice, and the digital competencies expected by HCPs. A multiple-case study was performed. Participants were the members of the Digital EducationaL programme invoLVing hEalth profEssionals (DELIVER), a project funded by the European Union under the Erasmus+ programme, involving three countries (Denmark, Italy, and Slovenia) and one autonomous region (Catalonia-Spain). Data were collected using two approaches: (a) a written interview with open-ended questions involving the members of the DELIVER project as key informants; and (b) a policy-document analysis. Interviews were analysed using the textual narrative synthesis and the word cloud policy analysis was conducted according to the Ready, Extract, Analyse and Distil approach. Results showed that all countries had established recent policies at the national level to address the development of digital health and specific governmental bodies were addressing the implementation of the digital transformation with specific ramifications at the regional and local levels. The words "health" and "care" characterized the policy documents of Denmark and Italy (309 and 56 times, 114 and 24 times, respectively), while "development" and "digital" (497 and 478 times, respectively) were common in the Slovenia document. The most used words in the Catalonia policy document were "data" and "system" (570 and 523 times, respectively). The HCP competencies expected are not clearly delineated among countries, and there is no formal plan for their development at the undergraduate, postgraduate, and continuing educational levels. Mutual understanding and exchange of good practices between countries may facilitate the digitalization processes; moreover, concrete actions in the context of HCP migration across Europe for employment purposes, as well as in the context of citizens' migration for healthcare-seeking purposes are needed to consider the differences emerged across the countries.

Background: Several scientific contributions have summarized the "lessons learnt" during the coronavirus disease 2019 (COVID-19) pandemic, but only a few authors have discussed what we have learnt on how to design and conduct research during a pandemic. The main intent of this study was to summarize the lessons learnt by an Italian multidisciplinary research group that developed and conducted a longitudinal study on COVID-19 patients infected during the first wave in March 2020 and followed-up for 3 years., Methods: A qualitative research approach embedded into the primary CORonavirus MOnitoRing study (CORMOR) study was developed, according to the the consolidated criteria for reporting qualitative research. Multiple data collection strategies were performed: each member was invited to report the main lessons learnt according to his/her perspective and experience from the study design throughout its conduction. The narratives collected were summarized and discussed in face-to-face rounds. The narratives were then thematically analysed according to their main topic in a list that was resent to all members to check the content and their organization. The list of the final "lessons learnt" has been agreed by all members, as described in a detailed fashion., Results: Several lessons were learnt while designing and conducting a longitudinal study during the COVID-19 pandemic and summarised into ten main themes: some are methodological, while others concern how to conduct research in pandemics/epidemics/infectious disease emergencies., Conclusions: The multidisciplinary approach, which also included patients' perspective, helped us to protect the consistency and quality of the research provided in pandemic times. The lesson learnt suggest that our research approach may benefit from changes in education, clinical practice and policies., (© 2023. The Author(s).)

Background: The aim of this study was to describe the long-term evolution of post-COVID-19 syndrome over 2 years after the onset of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in survivors of the first wave., Methods: This prospective study was based on interviews and investigated post-COVID-19 syndrome 6, 12, and 24 months after the disease onset in all adult in- and outpatients with COVID-19 followed at Udine Hospital (Italy) during the first wave (March-May 2020). Humoral response, vaccination status, and reinfection were assessed., Results: Overall, 230 patients (53.5% female; mean age 54.7 years) were interviewed 2.3 years (standard deviation = 0.11) after acute onset. Post-COVID-19 syndrome was observed in 36.1% of patients (n = 83) at 2 years. The most common persistent symptoms were fatigue (14.4%), rheumatological (14.4%), and psychiatric symptoms (9.6%). Overall, 55.4% (46 of 83) of long haulers searched for healthcare system support and 21 (45.7%) were visited by a specialist. Female gender (odds ratio [OR] = 2.50, P = .005), a proportional increase in the number of symptoms during acute COVID-19 (OR = 1.40, P = .001), and the presence of comorbidities (OR = 1.57, P = .004) were all independent risk factors for post-COVID-19 syndrome. Vaccination and reinfection had no impact on post-COVID-19 syndrome dynamics. The presence of receptor-binding domain (RBD) SARS-CoV-2 immunoglobulin G (IgG) and non-RBD SARS-CoV-2 IgG titers were not associated with the occurrence of post-COVID-19 syndrome., Conclusions: Two years after COVID-19, the burden of persistent symptoms remains high among in- and outpatients' population infected during the first wave. Post-COVID-19 dynamic does not seem to be influenced by SARS-CoV-2 immunization status and reinfection., Competing Interests: Potential conflicts of interest. MP reports receiving grants and personal fees from Pfizer, MSD, Menarini, and Dia Sorin outside of the submitted work. CT has received grants in the last 2 years from Correvio, Biotest, bioMerieux, Gilead, Angelini, MSD, Pfizer, Thermo Fisher, Zambon, Shionogi, Avir Pharma, and Hikma outside of the submitted work. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

COVID-19 survivors have been reported to be at risk of long-term neuropsychiatric sequalae; however, prospective evidence in this regard is lacking. We prospectively assessed the occurrence of mental-health-domain-related symptoms over a 24-month period following COVID-19 onset in a cohort of 230 patients. Of them, 36.1% were still presenting with at least one symptom 24 months later. Across the study period, a significant reduction in overall symptoms from the onset was observed ( p < 0.001); however, symptom prevalence was unchanged between the 12- and 24-month follow-ups across most symptomatic domains. At the 24-month follow-up, mental-health-domain-related symptoms only were higher than at the onset and were the most frequently reported symptoms. Dyspnea at the onset predicted both symptoms of psychiatric disorders (OR = 3.26, 95% CI = 1.22-8.70, and p = 0.019) and a lack of concentration and focus (OR = 3.17, 95% CI = 1.40-7.16, and p = 0.005) 24 months post-infection, with the number of comorbidities at the onset also predicting the occurrence of a lack of concentration and focus (OR = 1.52, 95% CI = 1.12-2.08, and p = 0.008). The findings of this study may have important public health implications, as they underlie the fact that COVID-19 survivors are still in need of neuropsychiatric support two years after infection.

Purpose/objectives: Clinical teaching in dentistry has cycled through specialty-based "departmental" teaching to group practice scenarios. The aims of this study were to ascertain third-year dental students' perceptions of a specialty-based rotation supplemented by online educational tools and to compare their Objective Structured Clinical Exam (OSCE) scores to those of the students in the previous year., Methods: This retrospective research design included the analysis of OSCE scores, and student responses to survey questions regarding their perceptions of the clinical oral pathology (COP) rotation. This study was completed in 2022. It included data from 2020 to 2021 and 2021 to 2022 corresponding to input from the Classes of 2022 and 2023, respectively. The response rate was 100%., Results: The students evaluated the focused COP rotation and the online teaching modules as a positive experience. The results of the OSCE were similar to those of the previous class and showed a high average score., Conclusions: This study shows that students had a positive perception to specialty-based learning with online educational tools and that it enhanced the education they received in the comprehensive care clinic. The OSCE scores were similar to those of the previous class. These findings suggest a method of maintaining high-quality dental education through challenges as it continues evolving., (© 2023 The Authors. Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Background: During the CoronaVIrus-19 (COVID-19) pandemic, nursing education has been dramatically transformed and shaped according to the restrictions imposed by national rules. Restoring educational activities as delivered in the pre-pandemic era without making a critical evaluation of the transformations implemented, may sacrifice the extraordinary learning opportunity that this event has offered. The aim of this study was to identify a set of recommendations that can guide the Italian nursing education to move forward in the post-pandemic era., Methods: A qualitative descriptive design was undertaken in 2022-2023 and reported here according to the COnsolidated criteria for REporting Qualitative research guidelines. A network was established of nine Italian universities offering a bachelor's degree in nursing for a total of 6135 students. A purposeful sample of 37 Faculty Members, 28 Clinical Nurse Educators and 65 Students/new graduates were involved. A data collection was conducted with a form including open-ended questions concerning which transformations in nursing education had been implemented during the pandemic, which of these should be maintained and valued, and what recommendations should address the transition of nursing education in the post-pandemic era., Results: Nine main recommendations embodying 18 specific recommendations have emerged, all transversally influenced by the role of the digital transformation, as a complementary and strengthening strategy for face-to-face teaching. The findings also suggest the need to rethink clinical rotations and their supervision models, to refocus the clinical learning aims, to pay attention towards the student community and its social needs, and to define a pandemic educational plan to be ready for unexpected, but possible, future events., Conclusions: A multidimensional set of recommendations emerged, shaping a strategic map of action, where the main message is the need to rethink the whole nursing education, where digitalization is embodied. Preparing and moving nursing education forward by following the emerged recommendations may promote common standards of education and create the basis on for how to deal with future pandemic/catastrophic events by making ready and prepared the educational systems., (© 2023. The Author(s).)

Background: A large variety of oral anticancer agents have become available and while at first glance these therapies appear to provide only benefits, patients have expressed their need for educational interventions and raised safety issues. Although both patients and providers have recognized patient education's importance, and an interplay with safety has been acknowledged, no systematic reviews of the literature that summarize all of the current evidence related to patient education's outcomes for patients who receive oral anticancer agents have been performed to date. Accordingly, this systematic review will attempt to fill the gap in the literature as well as to map (1) contents, (2) methodologies, (3) settings, (4) timing/duration, and (5) healthcare professionals involved., Methods: This protocol is being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic review will be performed. Studies that targeted eligible adult patients (≥ 18 years old) in hospital, outpatient, and home settings, and reported patient education's outcomes for those taking oral anticancer agents will be included. Searches will be conducted in PubMed/MEDLINE, CINAHL, Embase, and Scopus, and gray literature will be also sought. Two researchers will screen the search results independently and blindly in two phases: (1) title/abstract screening and (2) full-text screening using the Rayyan AI platform. An electronic data extraction form will be implemented and piloted, and then, two trained data extractors will extract the data cooperatively. Thereafter, a quality appraisal will be conducted using the Critical Appraisal Tools from The Joanna Briggs Institute. The results will be analyzed, grouped, clustered into categories, and discussed until a consensus is reached. Emerging evidence will be synthesized narratively and reported in accordance with the synthesis without meta-analysis guidelines., Discussion: The systematic review's results will be relevant to (1) policymakers and management at an institutional level, and (2) for clinical practice, in an evidence-based paradigm, potentially leading to a quality improvement with respect to safety and patient satisfaction., Systematic Review Registration: PROSPERO CRD42022341797., (© 2023. The Author(s).)

Accumulating evidence indicates that the COVID-19 pandemic carries risks to psychological health and represents a collective traumatic experience with consequences at the social, economic, and health levels. The primary aim of this study was to collect ongoing COVID-19 survivors’ pandemic-related experiences as expressed through the use of metaphors; the secondary aim was to explore socio-demographic variables associated with the metaphor orientation as negative, positive or neutral. An observational follow-up survey was conducted and reported according to the STROBE guidelines. Patients ≥ 18 years, who were treated for COVID-19 during the first wave (March/April 2020) and who were willing to participate in a telephone interview were involved and asked to summarize their COVID-19 experience as lived up to 6 and 12 months in a metaphor. A total of 339 patients participated in the first (6 months) and second (12 months) data collection. Patients were mainly female (51.9%), with an average age of 52.9 years (confidence interval, CI 95% 51.2−54.6). At 6 months, most participants (214; 63.1%) used a negative-oriented metaphor, further increasing at 12 months (266; 78.5%), when they used fewer neutral-/positive-oriented metaphors (p < 0.001). At the 6-month follow-up, only three individual variables (female gender, education, and experiencing symptoms at the COVID-19 onset) were significantly different across the possible metaphor orientation; at 12 months, no individual variables were significantly associated. This study suggests increasingly negative lived experiences over time and the need for personalized healthcare pathways to face the long-term traumatic consequences of COVID-19.

. Transitioning Italian nursing education in the post-pandemic period: priorities in the light of lessons learnt., Introduction: Once back to normalcy, many nursing education activities have been restored without an in-depth analysis of which transformations enacted in the pandemic period should be maintained and valued., Aim: To identify priorities to effectively transitioning nursing education in the post-pandemic period., Method: Descriptive qualitative design. A network of nine universities involved 37 faculty members, 28 clinical nurse educators and 65 students/new graduates. Data were collected through semi-structured interviews; the main priorities reported in each university were combined to gain a global view., Results: Nine priorities emerged, including the need to: 1. reflect on distance learning to promote its complementary role to face-to-face teaching; 2. rethinking the rotations of clinical practical training by refocusing their aims, duration, and preferred settings; 3. understanding how to integrate the virtual and the in-presence learning spaces into the educational pathway; 4. continuing with inclusive and sustainable strategies. Considering that nursing education is essential, it is a priority to develop a pandemic education plan capable of guaranteeing its continuity in all circumstances., Conclusions: Nine priorities have emerged all considering the importance of digitalization; the lessons learnt, however, indicate the need to enact an intermediate phase capable of guiding towards the complete transition of the education in the post-pandemic era.

Background: Black men are more likely to be diagnosed with type 2 diabetes (T2D) compared to non-Hispanic White men, and this disparity increases among men over the age of 55. A growing body of literature demonstrates the critical role of gender in the management of health behaviors such as T2D and shows that male gender norms can conflict with healthy behaviors. These studies suggest that tailoring diabetes self-management interventions to address the needs of Black men may be critical to helping them to achieve optimal health outcomes. Further, our own research on Blacks with T2D found gender disparities in participation in diabetes interventions, with males participating at significantly lower rates than females. Peer leaders are trained lay individuals who are used to provide ongoing diabetes self-management support to people with diabetes, particularly in minority communities. However, despite studies showing that diabetes management interventions using peer leaders have been successful, the majority of peer leaders as well as the participants in those studies are women. The limited studies to date suggest that Black men with T2D prefer peer-led, male-to-male T2D programs, however, this research consists primarily of nonrandomized, small sample feasibility studies calling for additional studies to establish the efficacy of these approaches. The proposed study will develop and preliminarily validate the effectiveness of an adapted peer leader diabetes self-management support (PLDSMS) intervention designed to improve diabetes-related lifestyle and self-management behaviors in Black men (over 55) with T2D., Method: We propose to tailor an existing intervention by 1) our using male peers and 2) modifying the peer leader training content to focus on material appropriate for men. The proposed study includes a developmental phase (development of the intervention with expert feedback, followed by feasibility testing with Black men) and a validation phase [randomized clinical trial (RCT)]., Discussion: If successful, this study will lead to the development and dissemination of an intervention that will address the unique needs of Black men with T2D, helping them to achieve optimal diabetes self-management and health outcomes., Trial Registration: Registered at ClinicalTrials.gov with an ID NCT04760444 on February 17, 2021.

Coronavirus (severe acute respiratory syndrome coronavirus 2) outbreak is a public health emergency and a global pandemic. During the present coronavirus disease (COVID-19) crisis, telemedicine has been recommended to screen suspected patients to limit risk of exposure and maximise medical staff protection. We constructed the protective physical barrier with telemedicine technology to limit COVID-19 exposure in ED. Our hospital is an urban community hospital with annual ED volume of approximately 50 000 patients. We equipped our patient exam room with intercom and iPad for telecommunication. Based on our telemedicine screening protocol, physician can conduct a visual physical examination on stable patients via intercom or videoconference. Telemedicine was initially used to overcome the physical barrier between patients and physicians. However, our protocol is designed to create a protective physical barrier to protect healthcare workers and enhance efficiency in ED. The implementation can be a promising protocol in making ED care more cost-effective and efficient during the COVID-19 pandemic and beyond., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The coronavirus disease 2019, SARS-COV-2 (the cause of COVID-19), has led to a worldwide shortage of personal protective equipment (PPE) and an increased stress on hospital resources, which has resulted in a spike in the anxiety of the frontline healthcare workers. News reports and information about the virus are rapidly changing. We present a case of a patient with COVID-19 who had a seizure-like spell for which an EEG was performed. In early to mid-March, there were no clear guidelines or recommendations available from neurodiagnostic-related organizations or hospitals on how to adapt procedure workflow to those with COVID-19. When caring for COVID-19 patients, as when caring for any patient with an infectious disease, it is hospital protocol to follow contact, droplet/airborne precautions by wearing appropriate PPE. However, because we knew very little about the coronavirus, this case was different. In this article, we discuss our experience with our EEG workflow and concerns for staff exposure. We then discuss our adaptations and modifications to our standard procedures and protocols. A time analysis comparing our standard EEG protocol with our modified COVID-19 protocol revealed a significant decrease in technologist exposure time (99 minutes versus 51 minutes), which theoretically would reduce the chance of virus transmission to our technologist. At this critical moment in time, we hope such modifications will allow us to continue delivering high quality patient care while optimizing resource utilization and above all keeping our technologists safe.

Importance: Interictal epileptiform discharges (IEDs) in electroencephalograms (EEGs) are a biomarker of epilepsy, seizure risk, and clinical decline. However, there is a scarcity of experts qualified to interpret EEG results. Prior attempts to automate IED detection have been limited by small samples and have not demonstrated expert-level performance. There is a need for a validated automated method to detect IEDs with expert-level reliability., Objective: To develop and validate a computer algorithm with the ability to identify IEDs as reliably as experts and classify an EEG recording as containing IEDs vs no IEDs., Design, Setting, and Participants: A total of 9571 scalp EEG records with and without IEDs were used to train a deep neural network (SpikeNet) to perform IED detection. Independent training and testing data sets were generated from 13 262 IED candidates, independently annotated by 8 fellowship-trained clinical neurophysiologists, and 8520 EEG records containing no IEDs based on clinical EEG reports. Using the estimated spike probability, a classifier designating the whole EEG recording as positive or negative was also built., Main Outcomes and Measures: SpikeNet accuracy, sensitivity, and specificity compared with fellowship-trained neurophysiology experts for identifying IEDs and classifying EEGs as positive or negative or negative for IEDs. Statistical performance was assessed via calibration error and area under the receiver operating characteristic curve (AUC). All performance statistics were estimated using 10-fold cross-validation., Results: SpikeNet surpassed both expert interpretation and an industry standard commercial IED detector, based on calibration error (SpikeNet, 0.041; 95% CI, 0.033-0.049; vs industry standard, 0.066; 95% CI, 0.060-0.078; vs experts, mean, 0.183; range, 0.081-0.364) and binary classification performance based on AUC (SpikeNet, 0.980; 95% CI, 0.977-0.984; vs industry standard, 0.882; 95% CI, 0.872-0.893). Whole EEG classification had a mean calibration error of 0.126 (range, 0.109-0.1444) vs experts (mean, 0.197; range, 0.099-0.372) and AUC of 0.847 (95% CI, 0.830-0.865)., Conclusions and Relevance: In this study, SpikeNet automatically detected IEDs and classified whole EEGs as IED-positive or IED-negative. This may be the first time an algorithm has been shown to exceed expert performance for IED detection in a representative sample of EEGs and may thus be a valuable tool for expedited review of EEGs.

Importance: The validity of using electroencephalograms (EEGs) to diagnose epilepsy requires reliable detection of interictal epileptiform discharges (IEDs). Prior interrater reliability (IRR) studies are limited by small samples and selection bias., Objective: To assess the reliability of experts in detecting IEDs in routine EEGs., Design, Setting, and Participants: This prospective analysis conducted in 2 phases included as participants physicians with at least 1 year of subspecialty training in clinical neurophysiology. In phase 1, 9 experts independently identified candidate IEDs in 991 EEGs (1 expert per EEG) reported in the medical record to contain at least 1 IED, yielding 87 636 candidate IEDs. In phase 2, the candidate IEDs were clustered into groups with distinct morphological features, yielding 12 602 clusters, and a representative candidate IED was selected from each cluster. We added 660 waveforms (11 random samples each from 60 randomly selected EEGs reported as being free of IEDs) as negative controls. Eight experts independently scored all 13 262 candidates as IEDs or non-IEDs. The 1051 EEGs in the study were recorded at the Massachusetts General Hospital between 2012 and 2016., Main Outcomes and Measures: Primary outcome measures were percentage of agreement (PA) and beyond-chance agreement (Gwet κ) for individual IEDs (IED-wise IRR) and for whether an EEG contained any IEDs (EEG-wise IRR). Secondary outcomes were the correlations between numbers of IEDs marked by experts across cases, calibration of expert scoring to group consensus, and receiver operating characteristic analysis of how well multivariate logistic regression models may account for differences in the IED scoring behavior between experts., Results: Among the 1051 EEGs assessed in the study, 540 (51.4%) were those of females and 511 (48.6%) were those of males. In phase 1, 9 experts each marked potential IEDs in a median of 65 (interquartile range [IQR], 28-332) EEGs. The total number of IED candidates marked was 87 636. Expert IRR for the 13 262 individually annotated IED candidates was fair, with the mean PA being 72.4% (95% CI, 67.0%-77.8%) and mean κ being 48.7% (95% CI, 37.3%-60.1%). The EEG-wise IRR was substantial, with the mean PA being 80.9% (95% CI, 76.2%-85.7%) and mean κ being 69.4% (95% CI, 60.3%-78.5%). A statistical model based on waveform morphological features, when provided with individualized thresholds, explained the median binary scores of all experts with a high degree of accuracy of 80% (range, 73%-88%)., Conclusions and Relevance: This study's findings suggest that experts can identify whether EEGs contain IEDs with substantial reliability. Lower reliability regarding individual IEDs may be largely explained by various experts applying different thresholds to a common underlying statistical model.

Introduction: As the number of Alzheimer's disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E ( APOE ) results efficiently, safely, and effectively in the context of AD prevention trials., Methods: A multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer's Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials. The objective was to provide consistent information to research participants before and during the APOE counseling and disclosure session using standardized educational and session materials., Results: The Genetic Testing, Counseling, and Disclosure Committee created a process consisting of eight components: requirements of APOE testing and reports, psychological readiness assessment, determination of AD risk estimates, guidance for identifying providers of disclosure, predisclosure education, APOE counseling and disclosure session materials, APOE counseling and disclosure session flow, and assessing APOE disclosure impact., Discussion: The API Genetic Counseling and Disclosure Process provides a framework for large-scale disclosure of APOE genotype results to study participants and serves as a model for disclosure of biomarker results. The process provides education to participants about the meaning and implication(s) of their APOE results while also incorporating a comprehensive assessment of disclosure impact. Data assessing participant safety and psychological well-being before and after APOE disclosure are still being collected and will be presented in a future publication., (© 2019 The Authors.)

Introduction: Alzheimer's disease (AD) pathology, including the accumulation of amyloid beta (Aβ) species and tau pathology, begins decades before the onset of cognitive impairment. This long preclinical period provides an opportunity for clinical trials designed to prevent or delay the onset of cognitive impairment due to AD. Under the umbrella of the Alzheimer's Prevention Initiative Generation Program, therapies targeting Aβ, including CNP520 (umibecestat), a β-site-amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibitor, and CAD106, an active Aβ immunotherapy, are in clinical development in preclinical AD., Methods: The Alzheimer's Prevention Initiative Generation Program comprises two pivotal (phase 2/3) studies that assess the efficacy and safety of umibecestat and CAD106 in cognitively unimpaired individuals with high risk for developing symptoms of AD based on their age (60-75 years), APOE4 genotype, and, for heterozygotes ( APOE ε2/ε4 or ε3/ε4), elevated brain amyloid. Approximately, 3500 individuals will be enrolled in either Generation Study 1 (randomized to cohort 1 [CAD106 injection or placebo, 5:3] or cohort 2 [oral umibecestat 50 mg or placebo, 3:2]) or Generation Study 2 (randomized to oral umibecestat 50 mg and 15 mg, or placebo [2:1:2]). Participants receive treatment for at least 60 months and up to a maximum of 96 months. Primary outcomes include time to event, with event defined as diagnosis of mild cognitive impairment due to AD and/or dementia due to AD, and the Alzheimer's Prevention Initiative preclinical composite cognitive test battery. Secondary endpoints include the Clinical Dementia Rating Sum of Boxes, Repeatable Battery for the Assessment of Neuropsychological Status total score, Everyday Cognition Scale, biomarkers, and brain imaging., Discussion: The Generation Program is designed to assess the efficacy, safety, and biomarker effects of the two treatments in individuals at high risk for AD. It may also provide a plausible test of the amyloid hypothesis and further accelerate the evaluation of AD prevention therapies.

Nonconvulsive status epilepticus (NCSE) is present in multiple pediatric neurogenetic syndromes with epileptic encephalopathies. While intravenous (IV) medications are used inpatient for treatment of critical illness-related NCSE, there is no consensus on treatment of ambulatory NCSE. Up to 50% of patients with Angelman syndrome (AS) have NCSE with myoclonic or atypical absence status. Here we report our experience in pediatric patients with AS and NCSE treated outpatient with a tapering course of oral diazepam. We conducted a chart review of 104 patients seen in the Angelman Syndrome Clinic at Massachusetts General Hospital from January 2008 to March 2017, who met the criteria. Response to treatment was defined as cessation of NCSE symptoms with electroencephalogram (EEG) confirmation when possible. Twenty-one patients with NCSE were identified, and 13 patients (9 male) with 25 episodes of NCSE were included. Mean age at NCSE episode was 5years 4months (15months-12years). Six patients had one episode of NCSE, and 7 patients had recurrent episodes (mean: 2.7; range: 2-4). Median diazepam treatment was 6days (4-12days), with a mean dose of 0.32mg/kg/day divided over 2-3 administrations, decreased every 2days. Nine episodes required multiple courses; however, oral diazepam alone was ultimately successful in 80% (20/25) of NCSE episodes. Oral diazepam was well-tolerated with no major side effects. A short course of oral diazepam is well-tolerated and effective in patients with AS who have ambulatory NCSE. It may be considered prior to escalating to inpatient care in AS and possibly other epilepsy syndromes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women.Premenopausal women at increased risk for breast cancer received either 40 mg of atorvastatin or placebo for 1 year. Biomarker assessment was performed prior to initiation and at completion of study medication. MD was determined using both Breast Imaging Reporting and Data System and the visual analogue scale. Serum IGF-1 was determined by ELISA assay at the end of the study.Sixty-three women were enrolled between December 2005 and May 2010. Sixteen (25%) women withdrew. The mean age of participants was 43 (range, 35-50), 100% were white, and the average body mass index (BMI) was 26.4. The statin group demonstrated a significant decrease in cholesterol and low-density lipoprotein (LDL), suggesting compliance with study medication. After accounting for BMI, there was no difference in change in MD between groups. There was a significant increase in serum IGF-1 in the statin group.In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer, we did not see an effect of atorvastatin on MD. Further investigation of statins may be warranted; however, design of prior trials and potential mechanism of action of the agent need to be considered in the design of future trials. Cancer Prev Res; 9(5); 379-84. ©2016 AACR., (©2016 American Association for Cancer Research.)

Primary immunodeficiency disease (PIDD) with hypogammaglobulinemia is characterized by recurrent and severe bacterial infections and IgG replacement is the standard of care in many of these patients. Health-related quality of life (HRQOL) is becoming increasingly recognized as a factor that affects patient well-being and treatment preferences. In an effort to better understand what factors affect HRQOL in patients with PIDD, we reviewed the published literature that used standardized instruments for the measurement of HRQOL. We investigated HRQOL in PIDD patients compared with normal controls and patients with other chronic diseases; we also investigated the impact of treatment administration on patient satisfaction. The most commonly encountered health-related quality of life instruments were the child heath questionnaire parental form 50, short form 36, PedsQL 4.0, Lansky's play performance scale, and Life Quality Index. Patients with PIDD scored significantly lower on many of the instruments compared with normal controls. Also, while it appears that many patients appreciate home-based and subcutaneous IgG replacement therapy, patient satisfaction ultimately involves various clinical factors and individual patient preferences. By further analyzing what factors impact HRQOL, therapy adjustments can be made to maximize patient well-being and minimize disease impact on daily functioning.

Children with prenatal exposure to cocaine are at higher risk for negative behavioral function and attention difficulties, and have demonstrated brain diffusion abnormalities in frontal white matter regions. However, brain regions beyond frontal and callosal areas have not been investigated using diffusion tensor imaging (DTI). DTI data were collected on 42 youth aged 14-16 years; subjects were divided into three groups based on detailed exposure histories: those with prenatal exposure to cocaine but not alcohol (prenatal cocaine exposure (PCE), n=12), prenatal exposure to cocaine and alcohol (cocaine and alcohol exposure (CAE), n=17), and controls (n=13). Tractography was performed and along-tract diffusion parameters were examined for group differences and correlations with executive function measures. In the right arcuate fasciculus and cingulum, the CAE group had higher fractional anisotropy (FA) and/or lower mean diffusivity (MD) than the other two groups. The PCE group demonstrated lower FA in the right arcuate and higher MD in the splenium of the corpus callosum than controls. Diffusion parameters in tracts with group differences correlated with measures of executive function. In conclusion, these diffusion differences in adolescents with prenatal cocaine exposure suggest localized, long-term structural brain alterations that may underlie attention and response-inhibition difficulties., (Published by Elsevier Ireland Ltd.)

Background: Published structural neuroimaging studies of prenatal cocaine exposure (PCE) in humans have yielded somewhat inconsistent results, with several studies reporting no significant differences in brain structure between exposed subjects and controls. Here, we sought to clarify some of these discrepancies by applying methodologies that allow for the detection of subtle alterations in brain structure., Methods: We applied surface-based anatomical modeling methods to magnetic resonance imaging (MRI) data to examine regional changes in the shape and volume of the caudate and putamen in adolescents with prenatal cocaine exposure (n = 40, including 28 exposed participants and 12 unexposed controls, age range 14 to 16 years). We also sought to determine whether changes in regional brain volumes in frontal and subcortical regions occurred in adolescents with PCE compared to control participants., Results: The overall volumes of the caudate and putamen did not significantly differ between PCE participants and controls. However, we found significant (P <0.05, uncorrected) effects of levels of prenatal exposure to cocaine on regional patterns of striatal morphology. Higher levels of prenatal cocaine exposure were associated with expansion of certain striatal subregions and with contraction in others. Volumetric analyses revealed no significant changes in the volume of any subcortical region of interest, but there were subtle group differences in the volumes of some frontal cortical regions, in particular reduced volumes of caudal middle frontal cortices and left lateral orbitofrontal cortex in exposed participants compared to controls., Conclusions: Prenatal cocaine exposure may lead to subtle and regionally specific patterns of regional dysmorphology in the striatum and volumetric changes in the frontal lobes. The localized and bidirectional nature of effects may explain in part the contradictions in the existing literature.

Osteoporosis is expected to increase as our population pyramid shifts toward old age. It is associated with increased risk of fractures, leading to complications of limitation of ambulation, loss of independence, and chronic pain. Depression is also a common occurrence in the elderly population. Currently, up to 35% of residents in long term care may experience either major depression or clinically significant depressive symptoms. Selective serotonin receptor inhibitors constitute 62% of all antidepressant drug prescribing. Recently, serotonin transporters have been described in bone, raising the question of whether medications that block serotonin reuptake could affect bone metabolism and ultimately affect osteoporosis-related fractures. Current evidence suggests that depression, particularly in the setting of selective serotonin receptor inhibitors use, should be considered as an addition to the list of risk factors prompting clinicians to evaluate bone health status., (Published by Elsevier Inc.)