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Objective: This study aimed to assess the cost-effectiveness of the telemedically assisted post-discharge management program (DMP) HerzMobil Tirol (HMT) for heart failure (HF) patients in clinical practice in Austria., Methods: We conducted a cost-effectiveness analysis along a retrospective cohort study (2016-2019) of HMT with a propensity score matched cohort of 251 individuals in the HMT and 257 in the usual care (UC) group and a 1-year follow-up. We calculated the effectiveness (hospital-free survival, hospital-free life-years gained, and number of avoided rehospitalizations), costs (HMT, rehospitalizations), and the incremental cost-effectiveness ratio (ICER). We performed a nonparametric sensitivity analysis with bootstrap sampling and sensitivity analyses on costs of HF rehospitalizations and on costs per disease-related diagnosis (DRG) score for rehospitalizations., Results: Base-case analysis showed that HMT resulted in an average of 42 additional hospital-free days, 40 additional days alive, and 0.12 avoided hospitalizations per patient-year compared with UC during follow-up. The average HMT costs were EUR 1916 per person. Mean rehospitalization costs were EUR 5551 in HMT and EUR 6943 in UC. The ICER of HMT compared to UC was EUR 4773 per life-year gained outside the hospital. In a sensitivity analysis, HMT was cost-saving when "non-HF related costs" related to the DMP were replaced with average costs., Conclusions: The economic evaluation along the cohort study showed that the HerzMobil Tirol is very cost-effective compared to UC and cost-saving in a sensitivity analysis correcting for "non-HF related costs." These findings promote a widespread adoption of telemedicine-assisted DMP for HF., (© 2024. The Author(s).)

Introduction: The influence of medical dramas could extend beyond the realm of entertainment and potentially strengthen/orient the knowledge, attitudes and hopefully practice of health professionals and the public, despite often depicting unrealistic medical outcomes and scenarios., Methods: This study examined the portrayal of public health issues in two popular international medical series, "Grey's Anatomy" and "House, MD," selected for their awards and viewership ratings. Individual episodes were double-rated by clinicians for patient characteristics, public health issues, and infection risk management., Results: 94 episodes with 286 clinical cases were analyzed. A wide range of conditions and pathologies were depicted, with a focus on acute clinical events, trauma and mental disorders, which contrasts with real-life causes of hospitalization and highlight the dramatization in these series. Public health issues such as organ donation and substance abuse were frequently addressed, but prevention and health promotion received little attention. Proper use of personal protective equipment was mostly observed, although hand hygiene was underrepresented., Conclusion: The study highlights the dual role of medical dramas as an entertainment medium and a potential educational tool. While they can raise awareness and encourage healthier behavior, their portrayal of medical practices and patient care often deviates from reality and can create unrealistic expectations. The influence of these dramas also extends to viewers' perceptions of healthcare and medical professionals, underscoring the need for accurate and responsible portrayal of health issues in the media., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zago, Cautero, Scarpis, Pompili, Voglino, Siliquini, Brusaferro and Brunelli.)

Introduction: Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities., Methods: We performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides., Results: Pancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival., Discussion: PJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pulvirenti, Barbagallo, Putignano, Pea, Polidori, Upstill-Goddard, Cortese, Kunderfranco, Brunelli, De Simone, Pastorelli, Spaggiari, Nappo, Jamieson, Zerbi, Chang, Capretti and Marchesi.)

Background: Increasing work-related stress in academia can have an impact on physical and mental health. The aim of this study was to analyse the coping strategies of staff employed at the University of Udine and to verify whether sociodemographic data, professional position, and the presence of anxiety or depression symptoms are related to the use of different coping strategies., Methods: We conducted a cross-sectional study between June and December 2020 using the Brief COPE questionnaire. We correlated coping strategies with professional position, sociodemographic data, and the presence of anxiety or depressive symptoms measured with the Patient Health Questionnaire-9 and the General Anxiety Disorder-7., Results: A total of 366 people participated in the study, including 109 junior academics, 146 senior academics, and 111 administrative staff (response rate 23.6%). The three most frequently used coping strategies in terms of approach coping style were planning (6.77 ± 1.41), active coping (6.58 ± 1.45) and acceptance (6.23 ± 1.44). Women were more likely than men to report using approach and avoidant coping strategies (p < 0.001). Positive reframing and religion were most commonly used by administrative staff (p < 0.05), in contrast to junior academics, who were more likely to use substances and self-blame (p < 0.05). Anxiety was found to correlate with self-blame (OR 1.94) as a coping strategy, while depression was associated with venting (OR 2.83), self-blame (OR 3.27), and humor (OR 3.02)., Conclusion: Identifying profiles of coping strategies can help higher education institutions to implement support strategies for the academic community, ultimately promoting healthier lives and more effective teaching and research. Our study has shown that women and junior academics among staff at the Udine University would benefit from a tailored health promotion intervention that encourages the use of approach coping styles to reduce their risk of developing anxiety and depressive symptoms., (© 2024. The Author(s).)

MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells, and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl-nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.

In the realm of antenatal care, vaccinations serve as a cornerstone, crucial for safeguarding the health of both the mother and the fetus, while also extending protection to the newborn against communicable diseases. Nevertheless, vaccine adherence among pregnant women remains very low. The aim of our study was to evaluate the uptake of vaccines (influence, pertussis, and COVID-19) among women during pregnancy and to understand pregnant women's knowledge of vaccines and the diseases they protect against. The purpose was to investigate the reasons why pregnant women chose not to be vaccinated and to develop effective strategies for informing them about the importance of vaccination for both maternal and fetal safety. A prospective observational study was conducted in the Department of Obstetrics and Gynaecology, "Ospedale Santa Maria della Misericordia" in Udine, from 1 December 2021 to 30 June 2022. During this period, a self-completed paper questionnaire was administered to women at the end of pregnancy or during the puerperium. A total of 161 questionnaires were collected. Higher educational level was found to be significantly associated with influenza vaccination uptake ( p = 0.037, OR = 2.18, 95% CI 1.05-4.51). Similarly, for pertussis vaccination, adherence was mainly associated with higher educational level ( p = 0.014, OR = 2.83, 95% CI 1.24-6.47), but also with Italian nationality ( p = 0.003, OR = 3.36, 95% CI 1.56-8.43) and pregnancy attended by a midwife or private gynecologist ( p = 0.028, OR = 0.39, 95% CI 0.17-0.90). Regarding the COVID-19 vaccine, the only factor positively influencing uptake was Italian nationality ( p = 0.044, OR = 2.66, 95% CI 1.03-6.91). Women's fear that vaccines would endanger the fetus appeared to be the most important reason for refusing vaccinations. Simultaneously, patients also exhibited a desire to receive more information about maternal vaccination, particularly from their general physician or gynecologist. For this reason, it is imperative to enhance maternal vaccination counselling, making it a routine step in prenatal care from the first antenatal visit until the postpartum period.

Introduction: The potential for secondary use of health data to improve healthcare is currently not fully exploited. Health data is largely kept in isolated data silos and key infrastructure to aggregate these silos into standardized bodies of knowledge is underdeveloped. We describe the development, implementation, and evaluation of a federated infrastructure to facilitate versatile secondary use of health data based on Health Data Space nodes., Materials and Methods: Our proposed nodes are self-contained units that digest data through an extract-transform-load framework that pseudonymizes and links data with privacy-preserving record linkage and harmonizes into a common data model (OMOP CDM). To support collaborative analyses a multi-level feature store is also implemented. A feasibility experiment was conducted to test the infrastructures potential for machine learning operations and deployment of other apps (e.g., visualization). Nodes can be operated in a network at different levels of sharing according to the level of trust within the network., Results: In a proof-of-concept study, a privacy-preserving registry for heart failure patients has been implemented as a real-world showcase for Health Data Space nodes at the highest trust level, linking multiple data sources including (a) electronical medical records from hospitals, (b) patient data from a telemonitoring system, and (c) data from Austria's national register of deaths. The registry is deployed at the tirol kliniken, a hospital carrier in the Austrian state of Tyrol, and currently includes 5,004 patients, with over 2.9 million measurements, over 574,000 observations, more than 63,000 clinical free text notes, and in total over 5.2 million data points. Data curation and harmonization processes are executed semi-automatically at each individual node according to data sharing policies to ensure data sovereignty, scalability, and privacy. As a feasibility test, a natural language processing model for classification of clinical notes was deployed and tested., Discussion: The presented Health Data Space node infrastructure has proven to be practicable in a real-world implementation in a live and productive registry for heart failure. The present work was inspired by the European Health Data Space initiative and its spirit to interconnect health data silos for versatile secondary use of health data., Competing Interests: RM-O and GSc hold shares of telbiomed Medizintechnik und IT Service GmbH, where RM-O is also employed as CEO. LD was employed by Know-Center GmbH. SN, GSl, SP, and BP were employed by Tirol Kliniken GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baumgartner, Kreiner, Lauschensky, Jammerbund, Donsa, Hayn, Wiesmüller, Demelius, Modre-Osprian, Neururer, Slamanig, Prantl, Brunelli, Pfeifer, Pölzl and Schreier.)

Vaccine hesitancy has been included among the top ten threats to global health by the World Health Organization. Pharmacists can play a pivotal role in removing the individual barrier to vaccination, because of the relationship of trust they have with citizens and their ease of access. The aim of this study was to examine the impact of a pharmacy-based intervention to support the 2019 influenza vaccination campaign conducted in the Carnia district through one-to-one counseling. We analyzed data collected by pharmacists between 22 October 2019 and 20 January 2020, and trends in vaccination adherence in the context of the Local Health Authority and the entire province of Udine since 2016. The results showed that 77.2% of people who had not received an influenza vaccination in the previous year changed their minds about vaccination after receiving counseling. The pharmacy-based intervention improved influenza vaccination adherence in the target district (+13.4%), even when compared to the neighboring district of Gemona or considering the data in the broader local and provincial context, and this effect was particularly pronounced among those aged 65 to 74 years ( p < 0.01). Considering these findings, pharmacies should be more effectively involved in the provision of public health services aimed at improving accessibility, timeliness, and equity.

Sexually transmitted infections (STIs) are a major public health problem worldwide, with a high prevalence between the ages of 15 and 25 in most Western countries. High notification rates of chlamydia, gonorrhea, and syphilis are reported in the WHO European Region, with differences between countries. In Italy, the total number of STIs alerts increased by 18% from 2020 to 2021. HPV is the most common sexually transmitted infection; globally one in seven women is infected by this virus, and certain sexual behaviors are important risk factors for HPV-related cancers, particularly cervical cancer (CC), anogenital cancers and cancers of the head and neck. The burden of CC is relevant worldwide, in particular in Europe CC is the third leading cause of cancer-related deaths in women aged 15-44. This HPV-related tumor is preventable through a combined strategy of vaccination and screening for precursor lesions. In Italy, the coverage of organized screening varies from region to region and the average HPV vaccination rate is still far from the expected optimal threshold of 95% at the age of 12. To address the challenges of health promotion and HPV prevention, priority actions are needed such as: promoting education and information at every level, from schools to healthcare professionals. In Italy, education of adolescents on sexual and reproductive health, still remains critical, regionally inhomogeneous and much lower than in other European countries. Equitable measures need to be taken, and schools are an important place for health promotion activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Gazzetta, Valent, Sala, Driul and Brunelli.)

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME). In colorectal liver metastasis (CLM), TAM morphology correlates with prognosis, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger TAMs (L-TAMs). However, the metabolic profile of in vivo human TAM populations remains unknown. Multiparametric flow cytometry was used to freshly isolate S- and L-TAMs from surgically resected CLM patients (n = 14S-, 14L-TAMs). Mass spectrometry-based metabolomics analyses were implemented for the metabolic characterization of TAM populations. Gene expression analysis and protein activity were used to support the biochemical effects of the enzyme-substrate link between riboflavin and (lysine-specific demethylase 1A, LSD1) with TAM morphologies. L-TAMs were characterized by a positive correlation and a strong association between riboflavin and TAM morphologies. Riboflavin in both L-TAMs and in-vitro M2 polarized macrophages modulates LSD1 protein expression and activity. The inflammatory stimuli promoted by TNFα induced the increased expression of riboflavin transporter SLC52A3 and LSD1 in M2 macrophages. The modulation of the riboflavin-LSD1 axis represents a potential target for reprogramming TAM subtypes, paving the way for promising anti-tumor therapeutic strategies., (© 2024. The Author(s).)

The year 2023 marked the 60 th anniversary of screening newborns in the United States for diseases that benefit from early identification and intervention. All around the world, the goal of NBS is to facilitate timely diagnosis and management to improve individual health outcomes in all newborns regardless of their place of birth, economic circumstances, ability to pay for treatment, and access to healthcare. Advances in technology to screen and treat disease have led to a rapid increase in the number of screened conditions, and innovations in genomics are expected to exponentially expand this number further. A system where all newborns are screened, coupled with rapid technological innovation, provides a unique opportunity to improve pediatric health outcomes and advance children's rights, including the unique rights of sick and disabled children. This is especially timely as we approach the 100 th anniversary of the 1924 Geneva Declaration of the Rights of the Child, which includes children's right to healthcare, and the 1989 United Nations Convention on the Rights of the Child that expanded upon this aspect and affirmed each child's right to the highest attainable standard of health. In this manuscript, we provide background on the evolving recognition of the rights of children and the foundational rights to healthcare and non-discrimination, provide two examples that highlight issues to access and equity in newborn screening that may limit a child's right to healthcare and best possible outcomes, detail ways the current approach to newborn screening advances the rights of the child, and finally, propose that the incorporation of genomics into newborn screening presents a useful case study to recognize and uphold the rights of every child., Competing Interests: Conflict of Interest Statement: The authors declare no conflicts of interest and the funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Background: The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB)., Methods: Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. The histological amyloid load was quantified using two different staining methods., Results: Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13%) significantly correlated with Perugini score ( r  = 0.69, p  < .001) as well as with cardiac 99mTc-DPD uptake (planar: r  = 0.64, p  < .001; H/WB: r  = 0.50, p  = .014; SPECT/CT: r  = 0.53, p  = .008; H/CL: r  = 0.43, p  = .037) (results are shown for correlations with Congo Red-staining)., Conclusion: In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.

Pediatric ear, nose, and throat (ENT) surgery is very common, and its outcomes may improve with family education. In this regard, mobile health (mHealth) applications (apps), which are on the rise due to digital transformation, can be beneficial in healthcare. This study outlines the user-centered design and development of a mHealth app (version 5.15.0) to support family caregivers during the perioperative process of pediatric ENT surgery. Conducted over two years in an Italian maternal and child health hospital (January 2020-May 2022), the study employed a participatory design method based on the Information System Research (ISR) framework and guided by the principles of Slow Medicine. Utilizing the Relevance, Rigor, and Design cycles of the ISR framework, the mHealth app's content, functionalities, and technical features were defined and developed. A committee of fifteen experts guided the process with input from 25 family caregivers and 24 healthcare providers enrolled in the study. The mHealth app content was structured around five crucial educational moments characterizing the ENT perioperative period, providing evidence-based information on surgical procedures, strategies for preparing children for hospitalization and surgery, pain management, and post-discharge care. The mHealth app featured a function that sends customized notifications to guide caregivers at specific perioperative stages. The development of mHealth apps by implementing a rigorous, participatory, and Slow design process can foster accessible and family-centered information and care in the field of maternal and child health and beyond.

Background: Universities are critical in educating tomorrow's citizens and achieving the Sustainable Development Goals of the United Nations Organization. The aim of this study was to investigate the integration of these goals in the curricula of an Italian university., Study Design: Cross-sectional study., Methods: In February 2021, as part of the annual Syllabus preparation for each course, the teaching staffs at the University of Udine (Italy) were asked to complete an additional section in which they could indicate up to three Sustainable Development Goals for their courses. Descriptive statistics, Chi-square test and logistic regression were performed to determine whether the professors' sex, age, or department affected the likelihood of mentioning Sustainable Development Goals., Results: In 723 courses, 360/1040 professors 59% male, mean age 53 years (range 30-73), mentioned one (29%), two (23%), or three (31%) Sustainable Development Goals. No Sustainable Development Goals were mentioned in 16% of courses, the majority of which were from the Mathematical, Computer and Physical Sciences Department (58%). The top six Sustainable Development Goals quoted were: Good health and well-being (35%), Responsible consumption and production (22%), Quality education (17%), Industry, innovation and infrastructure (13%), Gender equality (13%), Decent work and economic growth (13%). The least frequently mentioned Goal was Life below water (1%). Women (p<0.0001) and senior professors (p=0.0148) were more likely to consider at least one of the Sustainable Development Goals, while Mathematical, Computer and Physical Sciences Department showed a negative correlation (p<0.0001)., Conclusions: Gaps were identified with respect to specific Sustainable Development Goals, but discrepancies between departments may indicate deficits in respondent awareness. A transparent description of the Sustainable Development Goals in courses is recommended, to increase students' and university's engagement in sustainability.

Clinical record (CR) is a tool for recording details about the patient and the most commonly used source of information for detecting adverse events (AEs). Its completeness is an indicator of the quality of care provided and may provide clues for improving professional practice. The primary aim of this study was to estimate the prevalence of AEs. The secondary aims were to determine the completeness of CRs and to examine the relationship between the two variables. We retrospectively reviewed randomly selected CRs of patients discharged from the Academic Hospital of Udine (Italy) in the departments of general surgery, internal medicine, and obstetrics between July and September 2020. Evaluation was performed using the Global Trigger Tool and a checklist to evaluate the completeness of CRs. The relationship between the occurrence of AEs and the completeness of CRs was analyzed using nonparametric tests. A binomial logistic regression analysis was also performed. We reviewed 291 CRs and identified 368 triggers and 56 AEs. Among them, 16.2% of hospitalizations were affected by at least one AE, with a higher percentage in general surgery. The most common AEs were surgical injuries (42.6%; 24) and care related (26.8%; 15). A significant positive correlation was found between the length of hospital stay and the number of AEs. The average completeness of CRs was 72.9% and was lower in general surgery. The decrease in CR completeness correlated with the increase in the total number of AEs (R = -0.14; P = .017), although this was not confirmed by regression analysis by individual departments. Our results seem to suggest that completeness of CRs may benefit patient safety, so ongoing education and involvement of health professionals are needed to maintain professional adherence to CRs., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The urgent transfer of an intensive care unit (ICU) is particularly challenging because it carries a high clinical and infectious risk and is a critical node in a hospital's patient flow. In early 2017, exceptional rainfall damaged the roof of the tertiary hospital in Udine, necessitating the relocation of one of the three ICUs for six months. We decided to assess the impact of this transfer on quality of care and patient safety using a set of indicators, primarily considering the incidence of healthcare-associated infections (HAIs) and mortality rates., Methods: We performed a retrospective, observational analysis of structural, process, and outcome indicators comparing the pre- and posttransfer phases. Specifically, we analyzed data between July 2016 and June 2017 for the transferred ICU and examined mortality and the incidence of HAI., Results: Despite significant changes in structural and organizational aspects of the unit, no differences in mortality rates or cumulative incidence of HAIs were observed before/after transfer. We collected data for all 393 patients (133 women, 260 men) admitted to the ICU before (49.4%) and after transfer (50.6%). The mortality rate for 100 days in the ICU was 1.90 (34/1791) before and 2.88 (37/1258) after transfer ( p  = 0.063). The evaluation of the occurrence of at least one HAI included 304 patients (102 women and 202 men), as 89 of them were excluded due to a length of stay in the ICU of less than 48 h; again, there was no statistical difference between the two cumulative incidences (13.1% vs. 6.9%, p  = 0.075)., Conclusion: In the case studied, no adverse effects on patient outcomes were observed after urgent transfer of the injured ICU. The indicators used in this study may be an initial suggestion for further discussion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brunelli, Miotto, Del Pin, Celotto, Moccia, Borghi, De Monte, Macor, Cocconi, Lattuada, Brusaferro and Arnoldo.)

Purpose: To describe variation in genomic medicine services across level IV neonatal intensive care units (NICUs) in the United States and Canada., Methods: We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium, requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services., Results: Overall response rate was 74% (32/43). Although chromosomal microarray and exome or genome sequencing (ES or GS) were universally available, access was restricted for 22% (7/32) and 81% (26/32) of centers, respectively. The most common restriction on ES or GS was requiring approval by a specialist (41%, 13/32). Rapid ES/GS was available in 69% of NICUs (22/32). Availability of same-day genetics consultative services was limited (41%, 13/32 sites), and pre- and post-test counseling practices varied widely., Conclusion: We observed large inter-center variation in genomic medicine services across level IV NICUs: most notably, access to rapid, comprehensive genetic testing in time frames relevant to critical care decision making was limited at many level IV Children's Hospitals Neonatal Consortium NICUs despite a significant burden of genetic disease. Further efforts are needed to improve access to neonatal genomic medicine services., Competing Interests: Conflict of Interest Monica H. Wojcik reports receiving compensation for consulting from Sanofi and Illumina and providing expert witness/consulting services in medical malpractice cases. All other authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: The phenomenon violence against health professionals has received increasing attention in recent years because of its frequency and significant impact on victims' mental health and disruption of health services. Despite this attention, little is known about the incidence of workplace violence in the highly politicized immunization services. Therefore, we decided to examine the prevalence of workplace violence in the COVID-19 immunization campaign, the risk and protective factors, and the impact on victims' mental health., Methods: Between March and April 2022, we conducted an anonymous online survey among health professionals working in COVID-19 vaccination centers in the Friuli-Venezia Giulia Region (Italy). We used the Questionnaire for Workplace Violence in Healthcare Settings and the Impact of Event Scale-Revised., Results: Of the 200 participants, 93 (46.5%) reported being victims of an act of violence during the vaccination campaign, 60 of them verbally and 7 physically. In 35.5% of cases, the IES score indicated a possible post-traumatic stress reaction in the victim. Opinions on measures to prevent violence and support workers in the workplace differed according to the sex of the health professional, with women emphasizing the need for self-defense training and improvement of security arrangements ( p < 0.001)., Conclusion: One-third of health professionals involved in the COVID-19 immunization campaign reported that their mental health was affected by workplace violence. Public health professionals dealing with politicized and debated issues such as immunization should receive more attention, as should the implementation of a more structured and multidisciplinary approach to the problem within healthcare organizations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brunelli, Scarpis, Lo Presti, Fiorillo, Campanella, Zuliani, Farneti, Croci, Pellizzari, Cocconi and Arnoldo.)

The availability of rapid genome sequencing (rGS) for children in a critical-care setting is increasing. This study explored the perspectives of geneticists and intensivists on optimal collaboration and division of roles when implementing rGS in neonatal and pediatric intensive care units (ICUs). We conducted an explanatory mixed methods study involving a survey embedded within an interview with 13 genetics and intensive care providers. Interviews were recorded, transcribed, and coded. Geneticists endorsed higher confidence in performing a physical exam and interpreting/communicating positive results. Intensivists endorsed highest confidence in determining whether genetic testing was appropriate, communicating negative results, and consenting. Major qualitative themes that emerged were: (1) concerns with both "genetics-led" and "intensivist-led" models with workflows and sustainability (2) shift the role of determining rGS eligibility to ICU medical professionals, (3) continued role of geneticists to assess phenotype, and (4) include genetic counselors (GCs) and neonatal nurse practitioners to enhance workflow and care. All geneticists supported shifting decisions regarding eligibility for rGS to the ICU team to minimize time cost for the genetics workforce. Exploring models of geneticist-led phenotyping, intensivist-led phenotyping for some indications, and/or inclusion of a dedicated inpatient GC may help offset the time burden of consenting and other tasks associated with rGS., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Newborn screening (NBS) aims to detect newborns with severe congenital diseases before the onset of clinical manifestations. Advancements in genomic technologies have led to proposals for the development of genomic-based NBS (G-NBS) in concert with traditional NBS. Proponents of G-NBS highlight how G-NBS could expand the number of diseases screened at birth to thousands and spur the development of new drugs and treatments for rare diseases. Balancing the excitement, some experts have pointed to the ethical dilemmas linked to G-NBS. The dialog, however, has yet to engage with sufficient urgency on how the new G-NBS might chart a course for improving the health of all children. Our analysis of more than 130 million births in the United States between 1959 and 1995 shows that traditional NBS led to improvements in infant mortality and health equity only when it was implemented in association with measures to improve healthcare access for children. We suggest that the new G-NBS will lead to better child health only when the same degree of attention devoted to genomic technologies will be directed to the promotion of public health measures that facilitate access to high-quality healthcare for all children., Competing Interests: L.B., H.S., and A.B. have no financial or personal relationships with other people or organisations to disclose., (© 2023 The Author(s).)

The United States has a highly sophisticated pediatric healthcare system and spends more than any other country per capita on children's healthcare. However, not all children have access to needed and affordable health care and the life expectancy and health outcomes of children in the country are worse than in any other industrialized nation. These nations typically offer universal healthcare for children as part of a robust recognition of a children's rights framework. In 1989 the United Nations adopted the Convention on the Rights of the Child that recognizes the right of the child to the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health. Currently the United States is the only United Nations member country that has not ratified the Convention on the Rights of the Child. This paper outlines the potential benefits of adopting a child rights approach based on the principles and provisions of the Convention on the Rights of the Child. The fact that countries who invest much less in healthcare compared to the United States can achieve better health outcomes provides the certainty that a solution is possible and within reach., Competing Interests: The authors have no conflicts of interest to disclose., (© 2023 The Author(s).)

Background: The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches., Methods and Results: Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5β1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models., Conclusions: This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Background: Genetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis., Methods: Clonal populations, obtained from both ovarian cancer cell lines (IGROV-1 and SKOV3) and tumor xenografts upon glucose deprivation, were defined as glucose deprivation resistant (GDR) or glucose deprivation sensitive (GDS) clones based on their in vitro behaviour. GDR and GDS clones were characterized using a multi-omics approach, including genetic, transcriptomic and metabolic analysis, and tested for their tumorigenic potential and reaction to anti-angiogenic therapy., Results: Two clonal populations, GDR and GDS, with strikingly different viability following in vitro glucose starvation, were identified in ovarian cancer cell lines. GDR clones survived and overcame glucose starvation-induced stress by enhancing mitochondrial oxidative phosphorylation (OXPHOS) and both pyruvate and lipids uptake, whereas GDS clones were less able to adapt and died. Treatment of ovarian cancer xenografts with the anti-VEGF drug bevacizumab positively selected for GDR clones that disclosed increased tumorigenic properties in NOD/SCID mice. Remarkably, GDR clones were more sensitive than GDS clones to the mitochondrial respiratory chain complex I inhibitor metformin, thus suggesting a potential therapeutic strategy to target the OXPHOS-metabolic dependency of this subpopulation., Conclusion: A glucose-deprivation resistant population of ovarian cancer cells showing druggable OXPHOS-dependent metabolic traits is enriched in experimental tumors treated by anti-VEGF therapy., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients' prognosis. The classification of macrophages into M1/M2 groups based on well-defined stimuli does not model the infinitely more complex tissue milieu where macrophages (potentially of different origin) would be exposed to multiple signals in different sequential order. This review aims to summarize the recent mass spectrometry-based (MS-based) metabolomics findings about the modifications of metabolism in TAMs polarization in different tumors. The published data shows that MS-based metabolomics is a promising tool to help better understanding TAMs metabolic phenotypes, although it is still poorly applied for TAMs metabolism. The knowledge of key metabolic alterations in TAMs is an essential step for discovering TAMs polarization novel biomarkers and developing novel therapeutic approaches targeting TAM metabolism to repolarize TAMs towards their anti-tumor phenotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De Simone, Soldani, Morabito, Franceschini, Ferlan, Costa, Pastorelli, Donadon and Brunelli.)

Diagnostic genome sequencing (GS) in newborns may have many benefits. More accurate diagnosis could spur the development of innovative genomic therapies. A precise diagnosis could help doctors and parents anticipate clinical problems and inform a family's future reproductive choices. However, the integration of GS into neonatal care remains associated with a variety of ethical controversies, including concerns about informed consent, about interpreting uncertain results, about resource allocation and whether access to genomic services could exacerbate health disparities, and about the effect of genome diagnostics on people with disabilities. There also remains significant uncertainty about which babies should be tested and when and how the potential benefits of GS ought to be measured. Probably related to these challenges, some payors have been reluctant to cover the cost of GS for critically ill newborns. Much of the reluctance appears to turn on questions about the clinical benefit associated with GS and whether and for whom GS will be cost-effective. These situations point to the urgent need for careful assessments of the clinical utility of GS in critically ill infants. In this paper, we critically examine the ways in which the clinical utility of GS has been evaluated in this patient population. We focus on "change of management" (COM), a widely used measure of clinical utility for diagnostic GS. We suggest that this measure is often ambiguous because not all COMs can be attributed to genomic results and because not all COMs lead to patient benefit. Finally, we suggest ways that measurement of clinical utility could be improved., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mendelian disorders are prevalent in neonatal and pediatric intensive care units and are a leading cause of morbidity and mortality in these settings. Current diagnostic pipelines that integrate phenotypic and genotypic data are expert-dependent and time-intensive. Artificial intelligence (AI) tools may help address these challenges. Dx29 is an open-source AI tool designed for use by clinicians. It analyzes the patient's phenotype and genotype to generate a ranked differential diagnosis. We used Dx29 to retrospectively analyze 25 acutely ill infants who had been diagnosed with a Mendelian disorder, using a targeted panel of ~5000 genes. For each case, a trio (proband and both parents) file containing gene variant information was analyzed, alongside patient phenotype, which was provided to Dx29 by three approaches: (1) AI extraction from medical records, (2) AI extraction with manual review/editing, and (3) manual entry. We then identified the rank of the correct diagnosis in Dx29's differential diagnosis. With these three approaches, Dx29 ranked the correct diagnosis in the top 10 in 92-96% of cases. These results suggest that non-expert use of Dx29's automated phenotyping and subsequent data analysis may compare favorably to standard workflows utilized by bioinformatics experts to analyze genomic data and diagnose Mendelian diseases.

Background: Otorhinolaryngology (ORL) surgery is common in children, but hospitalisation, surgery, and home care after discharge are stressful experiences for young patients and their family caregivers. Findings from literature highlight a lack of time in hospitals to support ORL surgery children and their caregivers through the perioperative process, along with the risks of caregivers' autonomous web or social media resources investigation. Therefore, this study aims to evaluate the effectiveness of a mobile health application with content to support ORL patients and their caregivers in the perioperative period to reduce caregiver anxiety and child distress compared to standard care., Methods: An open-label, two-arm randomised control trial design is being adopted. The intervention consists of a mobile health application with content to support ORL patients and their caregivers during the perioperative period. One hundred eighty participants will be enrolled and randomly assigned to the experimental group using the mHealth application or the control group. The control group receives standard information and education about the ORL perioperative period from healthcare providers orally or through brochures. The primary outcome is the difference between the intervention and control groups in preoperative caregiver state anxiety. Secondary outcome measures include children's distress before surgery and family preparation for hospitalisation., Discussion: The results of this study will be critical to the implementation of a new and safe model for the management of care and education in paediatrics. This model can achieve positive organisational and health outcomes by supporting continuity of care and empowering citizens to have informed participation and satisfaction in paediatric health promotion and management., Trial Registration: Trial identifier: NCT05460689 registry name: ClinicalTrials.gov. Date of registration: July 15, 2022. Last update posted: February 23, 2023., (© 2023. The Author(s).)

Heart failure is a common chronic disease which is associated with high re-hospitalization and mortality rates. Within the telemedicine-assisted transitional care disease management program HerzMobil, monitoring data such as daily measured vital parameters and various other heart failure related data are collected in a structured way. Additionally, involved healthcare professionals communicate with one another via the system using free-text clinical notes. Since manual annotation of such notes is too time-consuming for routine care applications, an automated analysis process is needed. In the present study, we established a ground truth classification of 636 randomly selected clinical notes from HerzMobil based on annotations of 9 experts with different professional background (2 physicians, 4 nurses, and 3 engineers). We analyzed the influence of the professional background on the inter annotator reliability and compared the results with the accuracy of an automated classification algorithm. We found significant differences depending on the profession and on the category. These results indicate that different professional backgrounds should be considered when selecting annotators in such scenarios.

Background: The daily increasing amount of health data from different sources like electronic medical records and telehealth systems go hand in hand with the ongoing development of novel digital and data-driven analytics. Unifying this in a privacy-preserving data aggregation infrastructure can enable services for clinical decision support in personalized patient therapy., Objectives: The goal of this work was to consider such an infrastructure, implemented in a smart registry for heart failure, as a comparative method for the analysis of health data., Methods: We analyzed to what extent the dataset of a study on the telehealth program HerzMobil Tirol (HMT) can be reproduced with the data from the smart registry., Results: A table with 96 variables for 251 patients of the HMT publication could theoretically be replicated from the smart registry for 248 patients with 80 variables. The smart registry contained the tables to reproduce a large part of the information, especially the core statements of the HMT publication., Conclusion: Our results show how such an infrastructure can enable efficient analysis of health data, and thus take a further step towards personalized health care.

Background: The aging population's need for treatment of chronic diseases is exhibiting a marked increase in urgency, with heart failure being one of the most severe diseases in this regard. To improve outpatient care of these patients and reduce hospitalization rates, the telemedical disease management program HerzMobil was developed in the past., Objective: This work aims to analyze the inter-annotator variability among two professional groups (healthcare and engineering) involved in this program's annotation process of free-text clinical notes using categories., Methods: A dataset of 1,300 text snippets was annotated by 13 annotators with different backgrounds. Inter-annotator variability and accuracy were evaluated using the F1-score and analyzed for differences between categories, annotators, and their professional backgrounds., Results: The results show a significant difference between note categories concerning inter-annotator variability (p<0.0001) and accuracy (p<0.0001). However, there was no statistically significant difference between the two annotator groups, neither concerning inter-annotator variability (p=0.15) nor accuracy (p=0.84)., Conclusion: Professional background had no significant impact on the annotation of free-text HerzMobil notes.

Background: The fight against fake news, mainly spread through Internet, is a major public health issue, even among undergraduate students. This study aims to evaluate the effectiveness of a website promoted by the Italian Federation of the Provincial Orders of the Medical Doctors as a first aid communication kit for health topics., Study Design: Pre-post study using a web-based survey, conducted in April-May 2019 on Medical students and October-November 2020 on Communication Sciences students at the University of Florence (Italy). Methods. Undergraduate students of both schools were exposed to the use of the "dottoremaeveroche" website. Primary and secondary outcomes measures: the Italian-electronic Health Literacy Scale self-assessment tool was used to examine subjects' electronic Health literacy, and source quality. All responses were rated on a 5-point Likert scale. Changing in perception of abilities were examined using the Wilcoxon test., Results: The 362 participants felt moderately confident in electronic Health Literacy, with an initial Italian-electronic Health Literacy Scale overall mean score of 3.6±0.7 for medical and 3.2±0.8 for communication students. Medical students had a good idea of how to find helpful sources (3.9±0.8) and communication students felt confident in recognizing their quality (3.5±1.0). In contrast, their confidence in using Web information to make health decisions was low (medical: 2.9±1.1; communication: 2.8±1.1). All items improved significantly after "dottoremaeveroche" use (p<.001), with the overall mean score of Italian-electronic Health Literacy Scale increasing to 4.3±0.6 for medical and 4.1±0.8 for communication students., Conclusions: Low electronic health literacy levels can affect public health efforts, as seen during the COVID-19 pandemic. The effectiveness of "dottoremaeveroche" among students showed the usefulness of online educational interventions that, if further implemented, could help combat the spread of infodemic.

Background: Several attempts have been made to introduce mHealth solutions to support maternal, newborn, and child health (MNCH). However, most of the available apps do not meet the needs of end-users, underscoring the urgency of involving them in the co-design of telehealth interventions., Objective: With this in mind, we investigated the needs and expectations of hospital-based health professionals (i.e., secondary users) providing care to pregnant women and new mothers with their babies for a hypothetical mHealth app to support the first 1000 days of life., Methods: From November 2021 to March 2022, we surveyed health professionals using a questionnaire that explored the perceived importance of specific content, functionalities, and technical features of the proposed app. We also collected sociodemographic information from secondary users. We performed descriptive analysis and then used Ward hierarchical clustering method to classify respondents according to their response patterns., Results: We recorded the needs and expectations of 145 hospital-based health professionals from obstetrics/gynecology, nursery/neonatology, and pediatrics. We found general agreement with the proposed content of the app, particularly general information about health during pregnancy (92%) and potential risky infections during pregnancy (91%). Three clusters emerged from the analysis, with the high and medium demanding clusters rating the importance of app content and technical features as very high and high, respectively, while low demanding cluster expressing more skepticism, especially about some of the proposed functionalities of the app., Conclusions: Assessing the needs and expectations of end-users is an essential process for developing tailored and effective mHealth solutions. This study has shown that hospital-based health professionals generally recognize the value of the proposed app, suggesting their propensity to integrate such a telehealth solution into mainstream clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Brunelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic was accompanied by the spread of uncontrolled health information and fake news, which also quickly became an infodemic. Emergency communication is a challenge for public health institutions to engage the public during disease outbreaks. Health professionals need a high level of digital health literacy (DHL) to cope with difficulties; therefore, efforts should be made to address this issue starting from undergraduate medical students., Objective: The aim of this study was to investigate the DHL skills of Italian medical students and the effectiveness of an informatics course offered by the University of Florence (Italy). This course focuses on assessing the quality of medical information using the "dottoremaeveroche" (DMEVC) web resource offered by the Italian National Federation of Orders of Surgeons and Dentists, and on health information management., Methods: A pre-post study was conducted at the University of Florence between November and December 2020. First-year medical students participated in a web-based survey before and after attending the informatics course. The DHL level was self-assessed using the eHealth Literacy Scale for Italy (IT-eHEALS) tool and questions about the features and quality of the resources. All responses were rated on a 5-point Likert scale. Change in the perception of skills was assessed using the Wilcoxon test., Results: A total of 341 students participated in the survey at the beginning of the informatics course (women: n=211, 61.9%; mean age 19.8, SD 2.0) and 217 of them (64.2%) completed the survey at the end of the course. At the first assessment, the DHL level was moderate, with a mean total score of the IT-eHEALS of 2.9 (SD 0.9). Students felt confident about finding health-related information on the internet (mean score of 3.4, SD 1.1), whereas they doubted the usefulness of the information they received (mean score of 2.0, SD 1.0). All scores improved significantly in the second assessment. The overall mean score of the IT-eHEALS significantly increased (P<.001) to 4.2 (SD 0.6). The item with the highest score related to recognizing the quality of health information (mean score of 4.5, SD 0.7), whereas confidence in the practical application of the information received remained the lowest (mean of 3.7, SD 1.1) despite improvement. Almost all students (94.5%) valued the DMEVC as an educational tool., Conclusions: The DMEVC tool was effective in improving medical students' DHL skills. Effective tools and resources such as the DMEVC website should be used in public health communication to facilitate access to validated evidence and understanding of health recommendations., (©Valentina Moretti, Laura Brunelli, Alessandro Conte, Giulia Valdi, Maria Renza Guelfi, Marco Masoni, Filippo Anelli, Luca Arnoldo. Originally published in JMIR Medical Education (https://mededu.jmir.org), 18.04.2023.)

Complete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age. Alterations in plasma lipid composition and in the kynurenine pathway of tryptophan metabolism were observed in the tie-stall-reared animals. The total plasma BDNF concentration was higher in tie-stall group compared to the two free-housing groups. Brain analysis of the tie-stall animals revealed a different mBDNF/proBDNF ratio, with a higher level of proBDNF ( p < 0.001). Our data are similar to previous studies on animal models of depression, which reported that inhibition of the conversion of proBDNF in its mature form and/or elevated peripheral kynurenine pathway activation may underlie cerebral biochemical changes and induce depressive-like state behavior in animals.

Background: Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to prioritize patients for WGS., Methods: Institutional databases of electronic health records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for rapid and whole genome sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a clinical natural language processing (CNLP) workflow with a machine learning-based prioritization tool named Mendelian Phenotype Search Engine (MPSE)., Results: MPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children's Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients., Conclusions: Our results indicate that an automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel., (© 2023. The Author(s).)

Introduction: Although several studies highlighted the psychological burden of 2019 coronavirus disease (COVID-19) pandemic, no data are available regarding professionals leading healthcare organisations. This study aims to assess the psychological impact of COVID-19 on healthcare leaders (HeLs), along with the leadership skills and coping strategies needed for successful leadership., Methods: A cross-sectional survey was conducted in Friuli-Venezia Giulia (Italy) between October and November 2020. We assessed the presence of depressive symptoms (DS), anxiety symptoms (AS), perceived stress (PS) and insomnia using internationally validated tools. Coping strategies and skills needed to overcome the crisis were examined, along with the most challenging phases., Results: A total of 48 HeLs participated. The prevalence of DS and AS was 14.6% and 12.5%, respectively. Moderate and severe insomnia was found in 12.5% and 6.3% of them, respectively. Leaders showed moderate (45.8%) and high 4,2%) level of PS. The two most challenging phases were recognised in early recognition (45.2%) and peak phase (31.0%). Concerning healthcare leaders' skills required to manage with pandemic, the most reported were communication (35.1%) and decision-making (25.5%)., Conclusion: The high level of PS, insomnia, DS and AS experienced by healthcare leaders shows the COVID-19 pandemic's psychological impact. The two most challenging phases identified enhances the importance of public health surveillance and monitoring systems, and communication appeared a critical success skill for healthcare leaders. Given the key role these professional play in addressing the current crisis in healthcare organisations, their mental health and well-being deserve greater attention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite improvements in the critical care management of subarachnoid hemorrhage (SAH), a substantial number of patients still suffer from disabilities. In most areas of the world, longitudinal follow-up is not routinely performed, and the patient's trajectory remains unknown., Methods: We prospectively collected data of 298 consecutive patients with spontaneous SAH and evaluated clinical trajectories at discharge, 3 months, and 1 year after SAH. In a subgroup of patients transferred to a local neurorehabilitation center (Rehab-Hochzirl), we studied the effects of rehabilitation intensity on clinical trajectories. Any decrease in the modified Rankin Scale (mRS) was defined as an improvement, with mRS ≤ 2 indicating good outcome. We used multivariate generalized linear models to investigate associations with clinical trajectories., Results: Out of the 250 surviving patients, 35% were transferred directly to Rehab-Hochzirl (n = 87 of 250; mRS at discharge = 4), 11% were transferred to another rehabilitation center (n = 27 of 250; mRS = 1), 1% were transferred to a nursing home (n = 3 of 250; mRS = 5), 21% were transferred to their country of origin (n = 52 of 250; mRS = 4), and 32% (n = 79 of 250; mRS = 1) were discharged home. Functional outcome improved in 57% (n = 122 of 215) of patients during the first 3 months, with an additional 16% (35 of 215) improving between 3 and 12 months, resulting in an overall improvement in 73% (n = 157 of 215) of survivors. After 1 year, 60% (n = 179 of 250) of patients were functionally independent. A lower Hunt and Hess scale score at intensive care unit admission, younger age, a lower mRS at intensive care unit discharge, fewer days on mechanical ventilation, and male sex were independently associated with better functional recovery. Although the subgroup of patients transferred to Rehab-Hochzirl were more severely affected, 60% (52 of 87) improved during inpatient neurorehabilitation., Conclusions: Our results indicate ongoing functional improvement in a substantial number of patients with SAH throughout a follow-up period of 12 months. This effect was also observed in patients with severe disability receiving inpatient neurorehabilitation., (© 2022. The Author(s).)

To improve maternal and child health, it is essential to adhere to health-promoting and preventive measures. However, reliable information as well as effective tools are not easy to identify in this field. Our cross-sectional study investigated the needs and expectations of expectant and new mothers and fathers as potential primary users of a hypothetical application supporting the first 1000 days of life. Between May and August 2022, we recruited expectant and new parents by administering an 83-item 5-point Likert scale questionnaire related to the content, functionalities, and technical features of the hypothetical app. We stratified responses using sociodemographic characteristics and then performed ward hierarchical clustering. The 94 women and 69 men involved in our study generally agreed with the proposed content, but expressed low interest in certain app functionalities or features, including those related to the interaction mechanism and interactivity. Women were generally more demanding than men. Our findings, resulting from the engagement of end-users, may be useful for designers and technology providers to implement mHealth solutions that, in addition to conveying reliable information, are tailored to the needs and preferences of end-users in the first 1000 days of life.

Flow injection analysis coupled with high-resolution mass spectrometry (FIA-HRMS) is a fair trade-off between resolution and speed. However, free software available for data pre-processing is few, web-based, and often requires advanced user specialization. These tools rarely embedded blank and noise evaluation strategies, and direct feature annotation. We developed EASY-FIA, a free standalone application that can be employed for FIA-HRMS metabolomic data pre-processing by users with no bioinformatics/programming skills. We validated the tool's performance and applicability in two clinical metabolomics case studies. The main functions of our application are blank subtraction, alignment of the metabolites, and direct feature annotation by means of the Human Metabolome Database (HMDB) using a minimum number of mass spectrometry parameters. In a scenario where FIA-HRMS is increasingly recognized as a reliable strategy for fast metabolomics analysis, EASY-FIA could become a standardized and feasible tool easily usable by all scientists dealing with MS-based metabolomics. EASY-FIA was implemented in MATLAB with the App Designer tool and it is freely available for download., Competing Interests: The authors declare no conflict of interest.

Background: Recent developments in eHealth and mobile health (mHealth), as well as the introduction of information and communication technology innovations in clinical practice, such as telemedicine, telemonitoring, and remote examinations, are already changing the current scenario and will continue to generate innovations in the coming decades. The widespread use of mobile devices, with an estimated nearly 30 billion devices and more than 325,000 apps worldwide, will provide various opportunities for people to take control of their own health. Already in 2017, most of the apps available were focused on pregnancy support, more than any other medical field. There have been some reported experiences with social media and mHealth that could benefit the promotion of maternal physical and mental health during pregnancy. However, many apps targeting the first 1000 days of a child's life do not consider the continuity between the prenatal and postnatal periods and their joint impact on maternal and child health. The aim of this study is to evaluate the effectiveness of this mHealth app to support women during the first 1000 days (from conception to 24 months of age) and to improve health prevention behaviours such as immunizations during pregnancy, weight gain during pregnancy, abstinence from smoking and alcohol consumption, and adherence to the routine childhood immunization schedule. In addition, the study aims to understand the level of appreciation of this mHealth app as a tool to overcome information and communication gaps between patients and institutions., Methods: Conduction of a randomized controlled trial., Discussion: Our results will be relevant for improving this mHealth app to promote health and prevention and to support the first 1000 days of life for both mother and child. Our results will be relevant to the future expansion of such an mHealth app to promote positive health-related outcomes in patients and co-user satisfaction and to support the organization of health services., Trial Registration: ClinicalTrials.gov NCT05500339., (© 2022. The Author(s).)

Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most common events in human cancers. Several efforts have been made toward the identification of selective PI3K pathway inhibitors. However, the success of these molecules has been partially limited due to unexpected toxicities, the selection of potentially responsive patients, and intrinsic resistance to treatments. Metabolic alterations are intimately linked to drug resistance; altered metabolic pathways can help cancer cells adapt to continuous drug exposure and develop resistant phenotypes. Here we report the metabolic alterations underlying the non-small cell lung cancer (NSCLC) cell lines resistant to the usual PI3K-mTOR inhibitor BEZ235. In this study, we identified that an increased unsaturation degree of lipid species is associated with increased plasma membrane fluidity in cells with the resistant phenotype and that fatty acid desaturase FADS2 mediates the acquisition of chemoresistance. Therefore, new studies focused on reversing drug resistance based on membrane lipid modifications should consider the contribution of desaturase activity.

Background: Rapid next-generation sequencing (NGS) offers the potential to shorten the diagnostic process and improve the care of acutely ill children. The goal of this study was to report our findings, including benefits and limitations, of a targeted NGS panel and rapid genome sequencing (rGS) in neonatal and pediatric acute clinical care settings., Methods: Retrospective analysis of patient characteristics, diagnostic yields, turnaround time, and changes in management for infants and children receiving either RapSeq, a targeted NGS panel for 4500+ genes, or rGS, at the University of Utah Hospital and Primary Children's Hospital, from 2015 to 2020., Results: Over a 5-year period, 142 probands underwent rapid NGS: 66 received RapSeq and 76 rGS. Overall diagnostic yield was 39%. In the majority of diagnostic cases, there were one or more changes in clinical care management. Of note, 7% of diagnoses identified by rGS would not have been identified by RapSeq., Conclusions: Our results indicate that rapid NGS impacts acute pediatric care in real-life clinical settings. Although affected by patient selection criteria, diagnostic yields were similar to those from clinical trial settings. Future studies are needed to determine relative advantages, including cost, turnaround time, and benefits for patients, of each approach in specific clinical circumstances., Impact: The use of comprehensive Mendelian gene panels and genome sequencing in the clinical setting allows for early diagnosis of patients in neonatal, pediatric, and cardiac intensive care units and impactful change in management. Diagnoses led to significant changes in management for several patients in lower acuity inpatient units supporting further exploration of the utility of rapid sequencing in these settings. This study reviews the limitations of comparing sequencing platforms in the clinical setting and the variables that should be considered in evaluating diagnostic rates across studies., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: SARS-CoV-2 spreads primarily through respiratory droplets of symptomatic individuals. With respect to asymptomatic individuals, there are conflicting results in the literature and a lack of studies specifically examining transmission in healthcare settings., Methods: The aim of this retrospective study, conducted in a northeastern Italian region, was to estimate the contagiousness of asymptomatic healthcare workers (HCWs) who tested positive for SARS-CoV-2. Asymptomatic HCWs who tested positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (rRT-PCR) at a regular screening nasopharyngeal or oropharyngeal swab between 1 February 2020 and 15 September 2020 were considered index cases. Contacts who were at high risk of infection and had follow-up swabs were included. Contacts were considered infected if they had a positive follow-up swab and/or symptoms associated with COVID-19 confirmed by a positive test within 14 days of exposure. Information was taken from records previously collected to identify contacts. Infectivity was estimated using the attack rate (AR) with a 95% confidence interval (95% CI)., Results: Thirty-eight asymptomatic HCWs who were positive at the screening swab and 778 contacts were identified. Contacts included 63.8% of colleagues, 25.6% of patients, 7.7% of family members and 3.0% of other contacts. Seven contacts tested positive for SARS-CoV-2 (AR: 0.91%, 95% CI: 0.89-0.93). Five of them were family members (AR: 8.3%), one was a colleague (0.2%) and one was a contact of other type (4.2%)., Conclusions: Viral spread by asymptomatic HCWs was less than in other settings. Identification of risk factors for transmission and reliable indicators of infectivity would be important to prioritize preventive measures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

The article provides a novel look at the links between salutogenesis, health promotion, and urban design supported by the findings of recent research on local high streets and their benefits for the well-being of older people. Salutogenesis and the related explanatory concept of sense of coherence (SOC) have provided a theoretical framework for developing healthy settings interventions, shifting the focus from exploring barriers and deficits to assets and resources in promoting people's health and well-being. While these concepts have informed policies and programmes at the level of regions and cities, no attempt has been made to establish more direct links with the disciplines devoted to the organization and design of the built environment at the scale of public spaces and streets. This article advances the idea that the main categories of SOC-comprehensibility, manageability and meaningfulness-have found application in urban design theory. Linking these categories with urban design concepts in a comprehensive framework, it is possible to guide interventions aimed at strenghtening well-being resources available in the public realm. This is corroborated by the findings resulting from a study of the well-being experiences of older people (n = 84) across a range of local high streets in the city of Edinburgh (UK) applying an innovative multi-methods approach. The discussion establishes the links between well-being benefits, SOC constructs and urban design concepts, and underscores the potential of the proposed framework to guide a design-oriented salutogenic approach to the built environment., (© The Author(s) 2022. Published by Oxford University Press.)

Inappropriate use of dietary supplements can be potentially harmful to patients, especially given the uncontrolled information on the Internet and social media. The role that pharmacists play in advising citizens and purchasing these products can help improve their safer use, but the knowledge, attitudes, and practices of these professionals on this topic are still largely unknown. Pharmacists in the Italian Region of Friuli-Venezia Giulia (FVG) were surveyed from September 2020 to February 2021 using a 54-item online questionnaire. The questions were related to knowledge, attitudes, and practice. Data on gender, age, work experience, degree, and function in pharmacy were also collected. 232 questionnaires were completed, predominantly by women (71 %). The majority of respondents had a degree in Pharmacy (77 %) and were employed in a pharmacy (66 %) where they had worked for at least 10 years (61 %). Pharmacists' knowledge was rated as low, with one-third of participants above the median; knowledge was higher among more experienced pharmacists. Larger knowledge gaps were noted regarding the potential carcinogenicity of multivitamin misuse and the undesirable presence of unlabeled ingredients in dietary supplements. Employees were more likely than owners to report purchasing dietary supplements at the direct request of patients (p < 0.05). The low level of pharmacists' knowledge about the use of dietary supplements is unsatisfactory, with concerning impact on patient safety. Young professionals in particular would benefit from continuous education to better advise patients. Nevertheless, the European regulatory framework for the manufacture, sale and post-marketing surveillance of dietary supplements needs to be strengthened., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)