The results showed that virtual leaders play a major role in determining information technology (IT) employees' job satisfaction while the mediating effects of both trust in leaders and work–life balance are significant factors that can enhance the work environment for leaders to achieve better results. The statistically significant findings of this research suggest a number of positive work outcomes and pathways with scholarly and managerial implications that can be beneficial for leaders in relevant sectors.Leadership remains a highly important role in the management of employees' psychological and physical well-being, particularly in the aftermath of the COVID-19 pandemic. As various sectors adapted virtual settings to overcome the restrictions posed by the pandemic, the vitality of virtual leaders became more pivotal as they could enhance the virtual work environment for employees and steer teams toward organizational goals. This study assessed the effect of virtual leaders on employees' job satisfaction in the information technology sector as a high-performance industry. Furthermore, the mediating effects of trust in leaders and work–life balance on the virtual leadership–job satisfaction relationship were assessed in the proposed model of this research. Through a deductive quantitative approach and using purposive and convenience sampling techniques, a total of 196 respondents participated in the research. The data analysis process was deployed  The current research aimed to examine the relationship between virtual leadership and job satisfaction as a topic of interest, especially during and after the occurrence of the COVID-19 global pandemic. The conduct of this study follows the recent string of studies in the literature that address leadership and its influence in the aftermath of a global crisis  marketing, data science and related businesses, legal advising, accounting, banking, management, and strategic consulting are high-performance demanding jobs that can be project-based with a large number of associated tasks  Can virtual leaders improve the job satisfaction of IT employees?; (b) Does trust in the leader mediate the relationship between virtual leaders and employees' job satisfaction?; and (c) Is there a mediating effect from work–life balance on the virtual leadership-job satisfaction linkage? The following sections include the theoretical framework of the research and hypotheses development, where the foundation of the study is described. The study is then followed by sections describing the research design, sampling procedure, and measurements. In this stage, data analyses were conducted and the results are presented. The study is then finalized with discussions of the findings, conclusions, and limitations/recommendations.Virtual workspaces are a key tool for modern businesses, especially in industries such as education, business and marketing, IT, and other high-performing sectors , communication has been negatively impacted. As previously noted, job satisfaction and work–life balance can significantly change with regard to virtual work situations and its management/leadership  addresses the existence of a conflict between one's role at work and the role outside work . Following the recommendations of Hair et al. , a samplThe leader treats me as an individual rather than just a member of a group”. On the same note, trust in the leader was adapted from the Organizational Trust Inventory (OTI) developed by Cummings and Bromiley  to measure the model accuracy of PLS, which are shown in t = 5.201), which indicated a significant linkage between virtual leaders and job satisfaction. While similar reports have been noted in the extant literature , which exhibited the mediating effect of trust in a leader, implying its significant influence on the outcomes of the workplace . This factor has been found to be highly influential in improving job satisfaction among employees in various sectors that can be categorized as high-performing industries, such as tourism, IT, and education . This suggested that WLB had a mediating effect on the relationship between virtual leaders and the job satisfaction of their employees. These findings demonstrated that employees could have a higher satisfaction level toward their demanding, specialized, and high-performing jobs through adequate leadership approaches  that take the wellbeing of their employees into consideration. This leads to the establishment of work settings that enable autonomy and the creation of balance among the domains of life for individuals. Notably, the p-values of all the hypotheses were below 0.05, implying their statistical significance. In addition, the NFI and SRMR values showed a model fit due to their value  in times of crises. Our results showed that the majority of the respondents were relatively young see  and requOur results showed the vital role played by trust in the leader in improving job satisfaction. This was in line with previous studies from different contexts, which can be beneficial for scholars and practitioners  to provide professional opportunities for staff. This can encourage growth and improve the job satisfaction of employees by paving future career opportunities. Leaders can engage in mentorship, counseling, and trust-building behavior with their staff in an individual manner to foster positive emotions through personalized care.As the data for this study were collected through a cross-sectional approach, future studies can deploy longitudinal data collection to account for variations in time as leaders introduce new elements in their virtual teams. Similarly, qualitative methods can provide a thorough understanding of the subject at hand by shedding light on themes and vital points from employee perspectives or leader perspectives. In addition, stress theories  can be integrated into future models to further examine the relevant factors and theoretical frameworks. Initiatives that specifically address trust can also be regarded in future studies due to the importance of this construct. The effect of the control variables of this research can be examined in different contexts. Furthermore, underlying mediator or moderator variables that can enhance virtual job satisfaction can be also examined to provide better solutions for virtual leaders.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/ participants or patients/participants legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.PF: supervision, contextualization, and initial draft. HA: final draft, data collection, and analysis. All authors contributed to the article and approved the submitted version.


Cancer patients and their caregivers have substantial unmet needs, that negatively impact the clinical outcome and quality of life. However, interventions aimed to address such needs are still suboptimal, failing to answer the recent healthcare call for the adoption of value-based models of care. In the case of incurable oncologic and hematologic cancers, a value-based model of care should plan advanced care on patients' needs and include the quality of death as an outcome. The integration of early palliative care into standard oncologic care for patients with advanced cancers represents a recent innovative model of assistance whose benefits for patients and caregivers are now widely recognized. The key elements underlying the reasons behind these benefits are the multidisciplinary collaboration (teamwork), an honest and empathetic communication between the early palliative care team, the patient, and the caregiver (rapport building), and the ability to detect changes in the physical/psychosocial wellbeing of the patient, along the whole disease trajectory (constant monitoring).This community case study documents the quantitative and qualitative results of a long term clinical and research experience in delivering early palliative care service to address both solid and blood cancer patients' and their primary caregivers' needs.Data showed decreased use of chemotherapy, blood transfusions and referral to intensive care units near the end of life; increased life expectancy; improved symptom burden and mood; increased frequency of goals-of-care and advanced care planning conversations. Hope perception among bereaved caregivers was associated with resilience and realistic expectations raising from honest communication with the early palliative care team and appreciation toward the model. Patients and caregivers perceived the possibility of a good death as realistic and not as an unlikely event as it was for patients and caregivers on standard oncologic care only. Gratitude expressions toward the model and the team were frequently identified in their reports and positively associated with communication and spirituality.These findings are discussed in the context of an updated literature review regarding value-based care and suggest that early palliative care integrated into standard oncology care may be considered as an effective model of value-based care. With the advances in oncologic treatments, life expectancy for patients diagnosed with cancer has increased ; howeverA large body of evidence attempted to assess and address needs in patients with cancer. However, implementation of effective interventions has been suboptimal and unmet needs still represent a challenge in oncology and even more in hematology .Mismatched care models that are inconsistent with patients' and caregivers' needs can potentially lead to poor clinical outcomes such as higher morbidity and mortality and reduced quality of life (QOL) as well as a high healthcare use and expenditure –8. This Value-based healthcare proposes the combination of medical skills with patients' values to obtain the best outcome at the lowest cost. It combines the highest level of technical-scientific data  with patient preferences, concerns, expectations, and influences  and the use of resources in order to obtain the greatest advantage for the population  , 10.Ideally, a value-based model of oncology care should assess unmet needs with a flexible approach. Indeed, cancer-related symptoms and patients' needs fluctuate along the whole disease trajectory , 11, 12 The unmet needs of patients can increase the level of caregiver burden , 18, leaIn this scenario, a “paradox” related to the value-based models of care emerges in relation to the situation of patients with incurable oncologic or hematologic cancers: if value is determined by the proportion between health outcomes and the resources used to obtain them, how can value be defined when the obvious outcome is death and not the recovery of the patient?A number of studies have described and identified connections between the concept of quality of care, QOL and, even, “quality of death and dying” e.g., –28]. The. The28)]More recently, an innovative model of assistance, consisting of the integration of palliative care to standard oncological care (SOC) since the diagnosis of incurable cancers, has resulted in improved physical and psychological symptoms, QOL and, even, QOL at end of life (QOL-EOL), suggesting a long-term benefit from interdisciplinary early palliative care (EPC) on care throughout the illness .We claim that in oncology, the integration of EPC to the SOC may represent a value-based model. EPC includes anticipated guidance about symptom management and thoughtful discussions on goals of care that engage individuals to consider their values and care preferences in a more patient-centered and less disease-centered environment than the standard oncologic care .In the following sections, the paper documents the experience of delivering EPC to solid cancer and blood cancer patients in two outpatient clinics in Italy. This description argues that EPC treatments can be considered as a form of value-based care in oncology and puts forward the hypothesis that EPC interventions could actually favor the combination of QOL, quality of care along all the disease trajectory, and the quality of death.The provision of EPC described in this paper takes place in two EPC units.The first is located at the Oncology and Palliative Care Unit of the Civil Hospital in Carpi, within the Local Health Unit in Modena; the second, at the EPC clinic of the section of Hematology, Azienda Ospedaliero Universitaria Policlinico, University of Modena and Reggio Emilia.In both units, the EPC program involves assessment and management of symptoms, support in decision making and future planning, facilitation of coping and providing physical and emotional support through periodic tutorial meetings with oncologists/hematologists and nurses, as well as the assessment of patients' prognostic awareness, which is considered a crucial element defining an EPC intervention .Patients commonly admitted at the Carpi Unit have advanced solid cancer, i.e., distant metastases, late-stage disease and/or a prognosis of 6–24 months . In ModeDespite the fact that it is not possible to identify a single reference model that explains all the possible EPC interventions and how they should be implemented , the oveThe crucial components of this model can be summarized with three keywords: teamwork, rapport building, constant monitoring. As for “teamwork,” this keyword refers to the style of care characterizing the collaboration between the SOC team and the EPC team: in this model, the two teams never stop cooperating. It also refers to the kind of work developed by the EPC team with all the other physicians and subspecialists involved in patients' care, in addition to other interdisciplinary team members that may be consulted if appropriate . Finally, it is the EPC team who involves the home-based services when discontinuation of disease-directed care is decided and routine oncology follow-ups cease.The second keyword, “rapport building,” is a complement to “teamwork” and, in a way, its precondition: rapport building between the EPC team, patients and their families is begun early on, at the very first encounter, during which focus is placed especially on coping and support. The team explores patients' and caregivers' understanding and expectations regarding the disease and palliative treatments; at this point, caregivers' needs are also addressed. The style of care in the EPC clinic aims at maintaining a supportive therapeutic atmosphere and building on rapport established during previous encounters. Thanks to this style of care, over time it is possible to progressively develop discussions about end of life (EOL) and resuscitation status, including in the discussion also patients' family members. Appropriate communication is clearly a fundamental ingredient for “rapport building.”“Constant monitoring” is at the same time possible because of rapport building and another one of its ingredients. Indeed, as previously mentioned, the needs of advanced cancer patients may change rapidly and the care team must be ready to assess them and decide appropriate interventions. The EPC intervention may entail from three to five visits in order to be considered completed, focusing on symptom management, coping, prognostic awareness, decision-making and EOL planning . A key eThe EPC units in Carpi and Modena operate largely based on the model described by Zimmermann et al.  and GreeThe study confirmed a favorable association between EPC intervention and the index of EOL aggressiveness represented by the administration of chemotherapy in the last 14, 30, and 60 days of life, respectively. Specifically, the frequency of chemotherapy use in the last 60 days of life was 3.4% in the early group and 24.6% in the delayed group. This result is in line with similar results reported in the literature , 38 and A similar observational, retrospective study was conducted at the Modena Unit, aiming to investigate the presence of quality indicators for palliative and EOL care on 215 patients affected by acute myeloid leukemia. All patients were on palliative care, which was defined early when patients received three or more visits or delayed when patients received only one or two visits. Patients with acute promyelocytic leukemia and those undergoing allogeneic hematopoietic stem cell transplantation were excluded. Indicators were abstracted through a comprehensive review of their hospital chart . The resIn relation to the interventions in Carpi and Modena, there are other three studies worth mentioning because they further explore benefits deriving from the EPC interventions as implemented in these two units. More specifically, these studies explore the perceptions of hope and death and the emergence of gratitude in patients and caregivers recruited in both units between July 2020 and June 2022. Patients involved in the studies had advanced cancer whereas caregivers had an alive and/or a deceased patient with advanced cancer. Their eligibility required at least four visits at the EPC unit, willingness to complete the task, and age ≥18 years. At the time of the enrollment, patients had a life expectancy of more than 6 months and were not on interim evaluations to be referred to hospice or home care. The relevance of these studies is explained by the fact that the way patients and caregivers perceive hope and death, as well as the positive emotions arising, although unsolicited, after the EPC intervention, can make a huge difference on their QOL and quality of death and dying; moreover, there is a substantial lack of studies exploring these dimensions qualitatively and based on patients' and caregivers' perceptions , 39.n = 26, caregivers of solid tumor patients) and at the Modena Unit . Open-ended questionnaires asking about caregivers' experience with EPC were administered to participants, 2 months to 3 years after a patient death. Definitions of hope in the caregivers' narratives were analyzed through a directed approach to content analysis  and their caregivers  describing their clinical experience with the EPC model were analyzed through a content analysis and a quantitative text analysis program, to identify and rank the sources of gratitude and to quantify the use of words associated to categories of interest , respectively. The presence of explicit or implicit expressions of gratitude were found in most of the reports . Moreover, the identified sources of gratitude were structural components of the EPC intervention, namely: successful physical symptom management (mentioned by 83.5% of patients and 78% of caregivers), emotional support (mentioned by 46.6% of patients and 39% of caregivers), empowerment from the conversations on EOL (mentioned by 33.8% of patients and 11% of caregivers), better information (mentioned by 24.1% of patients and 22% of caregivers), humanity (mentioned by 24.1% of patients and 22% of caregivers), and a familiar environment (mentioned by 12% of patients and 14.4% of caregivers). Finally, the emergence of gratitude in patients' reports was positively associated with references to communication with the palliative team  as well as to spirituality . These results suggest that EPC and the associated benefits would unintentionally elicit positive emotions that, based on the positive psychological wellbeing  may be different from the one that is called for in other clinical settings (mainly QOL), a certain approach to care could be used as a model to progressively implement a value-based model of care along the entire trajectory of the disease.Future research in this area should also focus on grounding the EPC model in a theoretical frame. Each intervention provided in the EPC context and described in this work arises from a large amounts of empirical, real-life data, in a bottom-up fashion. However, its robustness and validity require to be supported and further confirmed also through a top-down approach in order to define a univocal model whose use can be extended to different onco-hematology populations. This would be beneficial to the model, also in terms of the flexibility required to support different types and different stages of the disease, but also to be extended to most medical specialties dealing with serious illnesses and close to the EOL.We acknowledge that the model described in this article may be difficult to implement due to a few conceptual and methodological constraints.As for conceptual constraints, it has been observed that the integrated EPC model of care has been described only in a standardized form, thus leaving it to professionals to devise specific strategies that will allow its implementation in local systems .In a methodological perspective, a significant constraint is represented by the limited awareness still observable in the population regarding the existence of EPC clinics; moreover, oncologists' hesitancy to refer patients to palliative care and specific training for clinicians may also hinder the implementation of the proposed model of care , 83.https://www.gazzettaufficiale.it/eli/gu/2020/08/31/216/sg/pdf), beginning in the academic year 2021–2022 (Regarding the situation in Italy, where the case study described in this article was developed: of note, following the conversion of the law decree of May 19, 2020 into law, the Specialty School in Medicine and palliative care has been created (021–2022 . A more 021–2022 , 86.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.All authors contributed to conception and design, bibliography review and data analysis and interpretation, manuscript writing, and final approval of manuscript.


This is the first study investigating the differences in psychological and physical distress between parents  of oncopediatric children using the Network analysis (NA). We also used the Kellner Symptom Questionnaire (SQ) for the first time with parents of cancer-diagnosed children. SQ data were analyzed using traditional statistical techniques  and NA, an innovative technique which captures the complex interaction of core and environmental variables shaping the behavioral phenotype. Our concise yet effective measures provided a detailed understanding of distress levels, differentiating between psychological symptoms and well-being indicators for mothers and fathers.Background: Pediatric cancer presents mental and physical challenges for patients and their caregivers. However, parental distress has been understudied despite its negative impact on quality of life, disability, and somatic disorders. Parents of oncopediatric patients experience high levels of suffering with their resilience tested throughout their children’s illness. Identifying at-risk parents and offering specific treatments is crucial and urgent to prevent or alleviate negative outcomes. Methods: This study used statistical and network analyses to examine symptom patterns assessed by the Kellner Symptom Questionnaire in 16 fathers and 23 mothers at different time points: diagnosis, treatment, and discharge. Results: The results indicated significantly higher distress levels in parents of oncopediatric children compared to the control reference population. Gender-specific differences in symptom profiles were observed at each time point, and symptoms showed a gradual but non-significant decrease over time. Conclusions: The network analysis yielded valuable insights that, when applied in clinical practice, can guide the implementation of timely treatments to prevent and manage parental distress, thus addressing long-term, stress-related issues in primary caregivers of children diagnosed and treated for cancer. Pediatric cancer is a complex disease that requires continuous care and therapy  and ofteAlthough parental distress resulting from a child being diagnosed with and treated for cancer is associated with reduced quality of life, functional disability, and an increased risk of somatic disorders, this aspect has often been overlooked and/or under-studied .Importantly, in a high proportion of parents of oncopediatric children, an association between the reported negative psychological effects and the time of diagnosis has been observed ,5,6, whiTherefore, studies aimed at analyzing and reducing the degree of distress in parents of pediatric patients are both necessary and urgent in order to allow healthcare professionals to identify, in a timelier manner, the individuals and families most at risk for the psychological and physical consequences of such a distressing and challenging situation .To achieve this goal and promote a better quality of life for the family, it is essential to know and assess the parents’ needs, especially at the time of diagnosis, and continue to monitor these needs during the child’s therapeutic iter . Moreover, to provide tailored preventive interventions and more individualized strategies, it is important to investigate the differences in distress between mothers and fathers of children with cancer, because if their way of expressing their distress is different, we will be better equipped to assist and intervene. Unfortunately, to date, very few studies investigated maternal and paternal differences in responding and coping with the stress associated with their children being diagnosed with cancer. This is mainly due to the fact that the statistical analyses, typically adopted in medical research, allow the analysis of the interaction of only a few variables at a time .The role of parents in caring for their sick children is crucial, as they are directly involved in their children’s care and face many challenges and issues. Thus, it is important to identify the pressing needs of parents of sick children so that healthcare institutions can offer them comprehensive support as part of the care process. Psychologists have a fundamental role in managing young patients and their families and are often involved in assisting interdisciplinary cancer treatment teams, contributing to research, policy, and practice guidelines. Thus, in this complex scenario, psychologists are called to offer timely and effective interventions to improve the quality of life of parents of children diagnosed with cancer, to respond to their common unmet psychological and physical needs by paying attention to the physical and psychological difficulties they might display.With these premises in mind, in this study, we tried to fill these gaps.By recurring to PICO analysis as a standard method for the elaboration of clinical questions , in this(1)What are the specific areas in which parents’ experiences heightened vulnerability compared to the general population? How can these areas be effectively examined and studied?(2)Are there notable differences between mothers and fathers regarding their psychological responses to this highly stressful situation?(3)How do these risk factors vary over the course of time from cancer diagnosis to three months after diagnosis? Are there any discernible gender differences in the experience?(4)How can the findings of this study be expanded and applied on a larger scale to benefit a broader population?Thus, recognizing the importance of implementing interventions to prevent or address parental distress when their children are diagnosed with cancer, during treatment, and after discharge, we posed several key questions:The purpose of addressing these questions was to acquire a deeper understanding of the specific challenges encountered by parents of children with cancer. By doing so, we aimed to expose potential gender differences regarding mothers’ and fathers’ responses, examine how risk factors evolve throughout the journey over the first three months, and lay the groundwork for a wider application of the study’s findings.Thus, by recurring to Kellner’s Symptom Questionnaire , we asseFurthermore, by adopting the network analysis, we investigated the maternal and parental phenotypes in coping with the stress associated with the diagnosis and treatment of cancer in their children. Thus, the data obtained from Kellner’s Symptom Questionnaire were analyzed using an integrated approach that combined classical statistical tools with network analysis. In this way, it was possible to study not only differences between parents of healthy (reference control) children and those of children suffering from cancer, but also to examine in a precise and predictive way if and how the psychological symptoms and well-being indexes vary between mothers and fathers of oncopediatric patients, over time.By generating a network of interconnected variables, we were able to study the complexity of interactions between the questionnaire’s symptom scales with other variables of interest, as well as to compare patterns of gender- and time-point-specific parental phenotypes .The first aim was to compare the levels of psychological and physical distress of parents at the time of diagnosis of the tumor of their child and investigate whether any differences existed compared to the Italian controls used in the validation of the Kellner’s Symptom Questionnaire. This allowed us to quantify the overall parental distress levels.The second aim of this study was to test the hypothesis that scores on the Kellner’s Symptom Questionnaire scales would change over time compared with the time of the child’s diagnosis. The time points for observing change were set at 1 and 3 months after diagnosis.The third aim of this study was to compare the scores of mothers and fathers at the various time points to analyze the presence/absence of gender differences in the evolution of psychological and physical distress from the diagnosis to three months into treatment.The fourth aim of this study was to implement an innovative Network Analysis allowing to study the relationships among the collected indexes and obtain a more comprehensive and complex view of the gender-specific symptom interaction of parental distress. The final endpoint was to individualize specific targets in order to direct psychological treatment and reduce negative outcomes.Specifically, the aims of this study can be summarized as follows: being parents of pediatric oncology patients at the time of diagnosis,initiation for the oncology patient of active inpatient/Day Hospital course of treatment,an expected course of treatment of at least 3 months at the facility where the study took place,being Italian-speaking or able to understand and speak Italian.Parents of children diagnosed with cancer were invited to participate in the study to assess their needs. Inclusion criteria were: the presence of a previous oncological diagnosis of the patient in care,history of psychiatric diagnosis in one or both parents,inability to adequately understand the Italian language,refusal to participate in the study or non-filling of informed consent.Exclusion criteria were:Parents were asked to participate in the study during their children’s hospitalization. Each invited person was informed about the purpose of the study. After obtaining informed written consent, subjects were asked to complete the questionnaire in paper version. Participants in the study were 23 parental, Italian, married couples of onco-Hematology pediatric patients. They were from central and southern Italy with schooling of eight years and above. Of these couples, the mothers had stopped working to handle and cope with their child’s diagnosis. None of the parents had previously been diagnosed with a psychiatric illness.Of these pairs, 16 completed the three time-points at which the Kellner’s Symptom Questionnaire was administered. Of the other 7 parent pairs, only the mothers took the questionnaire; the fathers did not want to participate in the study.The Statistical Power Test performed with a sample size of 16, maintaining a significance level of 0.05, and statistical power of 0.8 , returns an r = 0.63. This suggests that despite the small sample size, significant effects of considerable magnitude (r > 0.5) can still be identified. The effects reported in the study, therefore, are robust and firmly established within the examined sample. It is worth noting that a larger sample size might have revealed additional effects, particularly regarding the differences between mothers and fathers and the three different time points.The test was administered to the parent, by a certified psychologist, according to the timeline described in the protocol. The first survey was administered at a time close to the oncological diagnosis, maximum within 7 days, the second survey was administered one month after the first, and the third survey was administered three months after the first. Each parent was provided with a restitution of their test results at a discussion interview with the certified psychologist who had administered the test. The study was approved by the Ethics Committee of Policlinico Sant’ Orsola IRCCS (code: CE 118-2017-O-sper), and participating parents signed informed consent to participate in the study. All participants were provided with information regarding the study’s objective and their research rights, particularly regarding the fact that there were no consequences if they decided not to participate. Participation in this study was voluntary.Symptom Questionnaire (SQ) (Kellner 1987) [er 1987)  is a selFindings indicate that the SQ has highly sensitive clinimetric indexes and represents one of the most sensitive Patient-reported outcomes (PROs) measure available. The SQ provides clinical information that other similar scales fail to provide and that may supplement the data derived from interview methods  Supplem.A General Linear Model was performed to analyze differences among groups, as previously described ,22. Firsp < 0.05. Data were presented as mean ± standard error (SEM). All statistical analyses were performed using SPSS v. 26.0 , while graphs were generated using GraphPad Prism v. 9.00e for Windows® .We processed the parents scores of the 8 subscales of the Kellner’s Symptom Questionnaire  and compared with those of the reference sample  used for the Italian validation of the test, in terms of average mean and standard deviation. It was not possible to perform one-way ANOVAs because the data matrices of the Italian validation article are not available. Repeated-measures ANOVAs followed by Tukey’s post hoc tests were used to analyze the results between T1, T2, and T3, and to divide them according to gender . Subsequently, individual comparisons between T1 and T3 were made with one-way ANOVAs followed by Tukey’s post hoc tests. All tests were defined as significant at Network analysis and all tables related to them were computed with R software (version 4.0.3/2020-10-10). Network models were estimated by separating the individual parents (father and mother) and the times at which data were collected (T1-T2-T3). Six different networks were generated and visually compared before being analyzed for differences in centrality, the significance of edges, and the predictability of variables.mgm package [The  package ,24 was uMoreover, these relationships were controlled for all the other variables analyzed using the R software. The absence of a relationship between the two variables was indicative of their conditional independence given all the other variables. K-folds cross validation (10 folds) was applied to contain the number of false positives  and to choose the best tuning parameter in estimating network models, as reported by Jung et al. (2017) . By recuqgraph package was used [For plotting the resulting networks, the was used . The finwas used  by averaThus, the only variations were the edges between nodes. Importantly, the algorithm transforms the network into a system of particles having mass . TherefoNext, the predictability of each node in the network  was calculated and represented. This measure is a representation of the amount of variance of each variable that is explained by the other variables with which it has connections . In the Two measures were considered in the analysis: strength of centrality and betweenness ,31,32. TOn the other hand, betweenness is an index of how well a node/variable fits into the ‘shortest paths’ between other nodes in the network and determines which nodes facilitate the system’s connections the most . We recurred to the algorithm that calculates the ‘shortest paths’, as previously described by Dijkstra (1959) , implemeFinally, a clustering algorithm was executed to investigate the differences in connectivity patterns among the three groups from an alternative perspective. The clustering algorithm allowed us to identify a set of nodes that can be affected more quickly if one of them changes its state. Importantly, clusters are groups of nodes that are more interconnected within a larger network. We used the walk-trap algorithm, which measures similarities between nodes based on random walks across network connections (igraph package) , to captIn this study, we first analyzed the psycho-physical distress and well-being of the parents of children diagnosed with cancer and compared them with the reference sample  used for the Italian validation of the test . A totalAs shown in Interestingly, we found that the average score of the subscale ‘Anxiety’ at T1 also exceeded the values within the standard deviation of the control sample (4.25 ± 3.53). Unfortunately, it was not possible to perform statistical analyses between the results obtained from parents of oncopediatric patients and those of the control groups, as the use of the values extracted from Fava’s 1983 research did not allow access to the data matrix. However, these data suggest a highly stressful status in parents of children diagnosed with cancer . Furthermore, to highlight any differences in the parent’s reactions at different stages of the illness, we analyzed the trends of the symptoms over the three months following the diagnosis. Our working hypothesis was that there would be gradual reduction in the parent’s level of distress over time. Thus, to test our hypothesis we compared the mean scores of the four global scales of the SQ Test: Anxiety, Depression, Somatisation, and Hostility at the three time points.p = 0.025). None of the other scales  showed a significant decrease in suffering , revealed a significant effect only for the variable ‘anxiety’ in the reduction of the scale score between T1 and T3 (q = 3.85 uffering B.p = 0.014).Next, we investigated whether gender differences  could influence the symptomatology outlined by the Symptom Questionnaire. Thus, we compared the scores obtained between mothers and fathers. To make the comparison reliable, only the parental pairs who completed all assessments three times were taken into consideration . As shown in Subsequently, network analysis was performed to map how the Symptom Questionnaire scales interacted with each other. This innovative approach made it possible to make important considerations from an interventional perspective that normal statistical analyses would not have permitted. An additional, dichotomous variable considered in the network was the sex of the child. The decrease/increase in the size of a node among the three time points reflected the percentage difference between the Symptom Questionnaire scale scores. The description of the results of the network analysis was performed by separating the three-time points and comparing the two parents .At T1, we found an important role of Node 3  in mothers, because many connections passed through this node (Betweenness = 1). These data suggest that the influence of this scale/symptom may have an important impact on all other nodes in the network. The anxiety component primarily acted on Nodes 4 , 5 , 6 , and 7 . The partial correlations were positive. Thus, we concluded that a poor containment of anxiety may lead to more hostility, somatization, less relaxation, and an increase in the depressive component. On the other hand, in the fathers of children diagnosed with cancer, the most important nodes in the network were 7  and 8 , suggesting that at the time of diagnosis, interventions aimed at reducing the fathers’ anxiety may not be useful. In contrast, interventions promoting their sense of relaxation may be beneficial. Moreover, we found that Anxiety and Hostility were strongly connected.Conversely, our data suggest that 1 month after cancer diagnosis, in mothers, anxiety lost importance in driving information within the network. Moreover, Node 7  moved to the foreground, which was greatly influenced by Node 5 . Given these results, we investigated whether the sex of the child would play a role in the network. Interestingly, an important role of the sex of the patients in the network emerged, as suggested by the highest value of betweenness. In other words, depending on the gender of the patients, there were important interactions with the other variables. Additionally, Node 4  became important in fathers, as this node had an extreme centrality and directed the information of the whole network with positive connections between individual nodes. Increases in this node led to greater impairment in all the other domains. In general, the size of mothers’ and fathers’ nodes decreased . The only score that was higher than T1 was Hostility in fathers, which, in turn, was directly influenced by Anxiety (Node 3).Finally, we found that three months after their child was diagnosed with cancer, mothers and fathers displayed a decrease in the scores of all scales. Mothers’ improvements seem to be based on the interaction of symptoms on Node 7  and secondarily on depressive symptomatology . However, the network was still dense with connections, suggesting that a change in one node quickly influenced the other ones. Moreover, as all correlations were positive, our data suggest that an increase in anxiety, lack of relaxation, presence of somatization, or a downturn in mood are likely to, again, lead to a general worsening of the mother’s psychological condition. Alternatively, we found that in fathers, Node 3  was the most important node in the network, having a direct effect on all other nodes of the Symptom Questionnaire. These data suggest that, by keeping the father’s anxiety under control, it may be possible to avoid the exacerbation of the other risk factors.Finally, we performed cluster analyses . InteresTo our knowledge, this is the first study investigating the differences in psychological and physical distress between parents  of children diagnosed with cancer using Network analysis. Furthermore, we adopted the Kellner Symptom Questionnaire for the first time in a subclinical population, that is, parents of children diagnosed with cancer. We demonstrated that parents of pediatric oncology patients, at the time of diagnosis, show higher levels of psychological and physical distress than the Italian control population extracted from Fava’s research (1983) . www.salute.gov.it), the section dedicated to psycho-oncology acknowledges the substantial psychological and practical burden faced by caregivers. This burden is attributed to the significant amount of time dedicated to patient care  and the various tasks involved, such as transportation, providing moral and psychological support, interacting with the care team, managing daily activities, assisting with medical prescriptions, and ensuring personal care and hygiene. Regrettably, there is a lack of sufficient focus on developing treatment plans specifically tailored for family members of patients. The emphasis is predominantly placed on addressing the needs of the affected individuals themselves. Consequently, our study employed statistical and network analyses as a methodological approach to identify the areas of the Kellner Symptom Questionnaire that demand greater attention in this realm.Although the Symptoms Questionnaire was originally developed by Fava in 1983  , it has Our data illustrate that some subscales of psychological and physical distress undergo significant modification at the time of diagnosis. These subscales include Anxiety, Depression, Somatization, Relaxation, and Contentment. Another important element to consider is that no difference emerged in the levels of Hostility between parents whose children were diagnosed with cancer and the control population. On the Anxiety scale, the scores obtained by the subjects belonging to the research sample exceeded even the standard deviation of the controls, reaching a level that, according to the Italian validation of the test, can be defined as critical. The psychological symptoms of parents who have just been informed of their child having cancer seem to be limited to more typically anxious expressions. Although no statistical analyses have been performed to determine the significance of these results, a higher level of distress was displayed by parents of oncopediatric patients compared to the Italian reference population. Next, we compared the scores obtained on the Kellner Symptom Questionnaire at three different time points during the first three months: at diagnosis (T1), after one month of hospitalization due to the first cycle of therapies (T2), and after precisely three months after diagnosis (T3). Mothers and fathers showed an overall gradual reduction in the level of distress. Attention should be paid to the anxiety scale, which reported the highest values at the first time point but showed a significant decrease at T3. These data can be indicative of the so-called “Adaptation to Illness” phenomenon . In otheA central factor to be considered in the present study is that parents of the children who participated in this research had the opportunity to use various services offered by the Psychology, Psychopathology, and Psychotherapy Clinic of the Operating Unit within the department, both during hospitalization and Day Hospital treatment of their children. Thus, the decrease in the levels of distress and, consequently, improvement in the management of suffering was facilitated by the psychotherapeutic interventions timely provided, not only to the oncopediatric patients but also to their parents. These interventions included psychological and psychotherapeutic interviews and group play therapy. Moreover, support interviews, individual and family interviews, relaxation groups, psychotherapy, and therapies were provided, aimed to contain anxiety and other negative symptomatology, as well as enhancing the sense of self-awareness and self-efficacy.Consistent with previous studies, we found that at the time of diagnosis, there were no significant differences in the management of emotional suffering between mothers and fathers . HoweverAlternatively, in mothers, the levels of somatization increased at the time of discharge from the hospital , due to greater concerns caused by the lack of constant and present support from the healthcare staff.Despite the relevance of the data obtained, the results from the statistical analyses did not allow us to perform personalized preventive interventions. By employing the network analysis, we were able to obtain new perspectives and valuable insights into the interplay of symptoms among parents, as captured by the variables in the Symptom Questionnaire. The network approach provided us with essential tools to interpret and understand the complex interaction of symptoms within the parent population.Latent Disease Model” used for psychiatric disorders, which posits the existence of an underlying cause that “generates” the disorder. However, network analysis, as described by Borsboom in “A Network Theory of Mental Disorders”, considers psychiatric disorders as outcomes arising from the interactions between symptoms, which are represented as nodes within a network that influence each other [This approach differs from the more commonly known social network analysis and represents the interaction between psychological variables which, in the field of psychology, is a relatively recent development, only implemented around a decade ago. In contrast, social network analysis originated in the 1930s and primarily served as a methodology for studying groups. In psychology, the prevailing perspective still revolves around the medical model of the “ch other .Hence, the innovative aspect of our study lies in considering parental burden as an interaction among various dimensions  that mutually influence one another, resulting in a distinct pattern of distress. Instead of merely attributing parental stress to their child’s cancer diagnosis, we have examined the multifaceted nature of parental burden through a single questionnaire. This approach enabled us to identify the predominant facet of distress experienced by each parent, providing valuable guidance to clinical psychologists in tailoring treatments accordingly.In particular, we showed that it is not always the symptom with the highest score on the scale that is the most important in “driving” other symptoms and influencing them. This concept should always be considered when studying psychological suffering, as it is the result of a complex set of factors that are not often analyzed together . Thus, as clinicians are called to provide the best possible treatment given the state of the art, network analysis has proven to be a valid “clinical” tool that could be included as a support and guide for the prevention and treatment of complex conditions, as they can model the interaction between affective and neurocognitive aspects intrinsic to the person, as well as demographic and environmental variables. Despite the interesting findings and innovative approaches of this study, future studies are required to address some limitations of the current research. First, the experimental protocol, because of some common methodological difficulties in pediatric psycho-oncology research, such as the difficulty in establishing a fixed and well-defined setting or the need to respect medical timelines, might interfere with data collection. Furthermore, the fact that the study included an investigation into the experiences and psychological correlates of patients’ parents has made data recruitment more complex. There is a well-established practice, widely supported by the literature in psycho-oncology, of accompanying a patient’s medical treatment with psychological treatment. However, in the case of parents of oncopediatric children, there is sometimes greater resistance to addressing issues related to psychological distress. Research in this field, and other areas of healthcare practice, has made significant progress, but to define the problem more clearly, further experimental applications are needed alongside an already significant clinical effort. In addition, the small number of patients certainly led to less robust analyses but, particularly for networks, the bootstraps performed for network centrality indices were stable.Due to the highly stressful circumstances faced by parents following their child’s diagnosis, it was not feasible to recruit and engage them in extensive interviews or additional testing. Therefore, a rapid screening method was preferred to at least capture insights into a range of emotions and moods to assist them better and more efficiently. Although there were other variables that could have made a significant contribution to the analyses, dividing the already small sample further based on additional demographic factors would have reduced the statistical sensitivity. Despite the limitations, the fact that significant effects were found in such a small sample sets the foundation for potential future extensions of this pilot study, involving more parents. Subsequent studies, then, could incorporate additional demographic variables and employ various tests to examine parental psycho-affective patterns in greater detail.Also, the research project from which the study derives is still ongoing, and continuous administration of the questionnaire allows the collection of information that is now used by professionals in clinical practice to assist parents in managing their distress.In Italy, unfortunately, it is not yet common practice to comprehensively examine the components of parental distress when the child in the family is diagnosed with cancer, as the focus primarily remains on the child. However, we recently demonstrated the importance of exploring the interaction between psychosocial challenges and patient-related factors for understanding various disorders . In partThe findings from this Initial study serve as a starting point for a larger-scale multi-center study on a national level. The subsequent study will explore additional variables and aims to develop more targeted interventions that effectively mitigate the consequences of parental distress. By expanding the scope and depth of our present study in our future research efforts, we will be able to enhance our understanding and contribute to the development of more precise interventions to address the unique challenges faced by parents in the context of their child’s cancer diagnosis and treatment. The inclusion of parent-oriented care within pediatric oncology departments is crucial. Through the implementation of appropriate strategies, it will become possible to comprehend the specific needs of parents, respond to those needs in a positive manner, and provide effective care. By doing so, the aim is to minimize the needs of this vulnerable group and reduce the risks associated with unmet needs. Moreover, we aim to enhance the overall satisfaction and well-being of parents within the pediatric oncology setting. The ultimate goal will be to establish national guidelines for the personalized screening and treatment of parents with children diagnosed with cancer. The findings of this initial study lay the groundwork for a larger, nationwide multi-center study. This subsequent research endeavor will explore additional variables and aim to develop targeted interventions that effectively address the consequences of parental distress. By expanding the scope and depth of our current study in future research, we can enhance our understanding and contribute to the development of more precise interventions to meet the unique challenges faced by parents when their child is diagnosed with and undergoing treatment for cancer. It is crucial to incorporate parent-oriented care within pediatric oncology departments. By implementing appropriate screening and strategies, we can better comprehend the specific needs of parents, respond to those needs in a positive manner, and provide effective care. This approach aims to minimize the needs of this vulnerable group and reduce the associated risks of unmet needs. Furthermore, our goal is to improve the overall satisfaction and well-being of parents within the pediatric oncology setting. Ultimately, we strive to establish national guidelines for personalized screening and treatment of parents whose children have been diagnosed with cancer.Psychological research in oncology has traditionally focused on patient suffering, but there has been a growing recognition of the challenges faced by caregivers in recent years. In pediatric settings, parents are typically the primary caregivers for their children with cancer, which puts them in a demanding position of accompanying and sustaining their child throughout the illness. This responsibility gives rise to a complex range of emotional experiences that can lead to significant psychological distress.The objective of this study was to examine the intensity and characteristics of psychological distress in parents of children diagnosed with cancer. The findings underscore the importance of addressing the needs of parents from the early stages of the child’s illness.In this study, the Kellner Symptom Questionnaire was validated as a reliable tool for identifying specific areas of distress, particularly anxiety symptoms, in parents of children diagnosed and treated for cancer. The results of the test–retest analysis indicated that anxiety is the most prominent symptom immediately following the diagnosis, although it may not be the primary concern for both parents in shaping their psycho-affective framework. Gender differences did not significantly impact the results during the initial measurements taken after diagnosis. However, over time, as children received treatment in the day hospital setting, mothers consistently reported significantly higher scores on the somatization scale compared to fathers. The use of innovative techniques, like network analysis, provided insights into the distinct interactions of symptoms experienced by the two parents. Although anxiety was the most prominent variable at the time of diagnosis for both parents, it was specifically identified as the leading symptom among mothers. These findings suggest that supportive treatments should be tailored and personalized, taking into consideration the individual experiences of each parent.


Poultry mortality in the embryonic stage makes it difficult to achieve one of the main objectives of the poultry sector, i.e., constant increase in productivity. If well executed with safe and efficient substances, the in ovo injection technique can be an intervention alternative to enhance the development of more resistant, healthy, quality birds, with substantial positive effects on poultry production. For the commercial implementation of any intervention, information from the vast literature must be compiled in order to understand its effects on production parameters. Thus, this review aims to assess how injecting different substances in ovo influences hatching results, including the reported effects on embryo and chick health parameters. Bibliographic mappings of co-authorship of citations, co-occurrence of keywords and bibliographic coupling were also performed for articles based on the in ovo injection technique and hatchability.® software. This review provides a broad overview of just over 38 years’ research on the subject, revealing that studies have significantly increased and peaked in 2020, being produced primarily by US researchers and published primarily in the journal Poultry Science. It also reveals that despite negative reports relating to some substances in the embryo, in ovo delivery of substances may possibly change the poultry industry for the better in terms of production rates (hatchability) and/or poultry health.Recent advances in poultry practice have produced new tools enabling the poultry industry to increase productivity. Aiming at increasing production quality, varying protocols of in ovo injection facilitate the introduction of exogenous substances into the egg to complement the nutrients that support embryonic development up to hatching, which are already available in the internal and external compartments. Due to embryonic sensitivity, adding any substance into the egg can be either advantageous or disadvantageous for embryonic survival and can influence hatch rates. Thus, understanding the relationship between poultry practices and production rates is the first step towards successful commercial application. This review aims to assess the influence on hatch rates of injecting different substances in ovo, including effects on embryo and chick health parameters where these are reported. Bibliographic mappings of co-authorship of citations, co-occurrence of keywords, and bibliographic coupling based on the in ovo injection technique and hatchability parameters were also performed. Using the Scopus database, 242 papers were retrieved, reviewed, and submitted for bibliographic mapping using the VOSviewer Farmers collaborate with poultry scientists to achieve maximum production capacity and quality. Health is one of the foundations for sustaining productivity in the poultry industry and ensuring human safety. The guarantee of health requires continuous work with broad, diversified, and flexible solutions. These solutions must be protective or enhancing in nature, limiting damage to health and welfare, and/or improving poultry’s physical and physiological qualities.Hatchability designates the percentage of chicks hatched alive from a given sample of eggs. The hatchability rate is used worldwide by the poultry industry to monitor the productivity of each hatchery. The objective is to maintain this rate close to 100%. The greater the hatchability, the greater the guarantee that everything proceeded correctly throughout embryonic development. However, this is not a rule. Chicks that hatch with imperceptible or perceptible deformations can be counted in hatchability rates and are usually discarded before going to the farm, or may go to the farm but die shortly afterwards. Therefore, health and quality parameters must be analyzed along with hatchability to ensure high production and quality before and after hatching.This parameter is decisive in the advance or decline of poultry production, with significant economic effects. With the hatchability value, the hatchery can predict not only its own economic return, but also that of the production unit, considering the expected mortality rate at the hatch–slaughter interface. In addition, hatchability can serve as a solid reference to monitor and evaluate experiments performed directly on eggs, which can influence embryonic survival and support the identification of product deficiencies and solutions to overcome these. According to Gonzalez et al. , an imprAvian health before and after hatching depends on their exposure to egg nutrients, which include vitamins, minerals, lipids, carbohydrates, and proteins ,8. The bIn ovo injection is a practical solution that is revolutionizing poultry production due to its immediate beneficial effects during embryogenesis or post-hatch. Nevertheless, some harmful effects have been seen. While Subramaniyan et al.  reportedIn the present work, we reviewed published studies to determine whether the benefits in terms of hatchability outweigh the harm of injecting different substances in ovo, in relation to the influence of intrinsic or extrinsic factors. Bibliographic mappings of co-authorship of citations, co-occurrence of keywords, and bibliographic coupling relating to in ovo injection and hatchability parameters were also performed.The process of obtaining bibliographic information related to the in ovo injection technique and its effects on hatchability was divided into several steps .® software to generate connection/relationship networks between the authors, countries, and scientific journal sources of the published studies. VOSviewer® was used because it is a practical and easy-to-use software package with good graphic quality, which allows the analysis of metadata from different databases and has excellent integration and communication with the SCOPUS database [Scopus was used as a source of access to bibliographic data, as it is a reliable global database that stores important scientific data, including data relating to poultry sciences. The search keywords were defined based on the research objective. The number of research papers retrieved from Scopus and eligible for bibliometric analysis comprised 242 documents, covering just over 38 years. Inclusion criteria were research papers written and published in English, while exclusion criteria were all documents that did not meet the inclusion criteria . The database was extracted from Scopus in CSV Microsoft Excel format and processed with VOSviewerdatabase .Teratology. Comparing the decades 1991–2001 , 2002–2012 (18.37%), and 2013–2023 , it can be observed that from the first decade to the second, the numbers of published articles increased 3.5 times, from the first decade to the third 14.1 times, and from the second to the third the numbers increased 4.1 times. The number of publications on the topic increased from 10 in 2011, reaching a peak (n = 33 publications) in 2020. These findings show that the field of research has started to gain more recognition in recent years and that the quantity of research prior to 2010 was highly limited.The 242 papers on the in ovo injection technique and its effects on hatchability, selected and analyzed from 1 January 1985 to 14 January 2023, are shown in A paper with many citations is positive feedback for the group of researchers that developed it, demonstrating that it represents high-quality, relevant, and impactful work within the research area. It should be noted that it is not a rule that older studies are more frequently cited than more recent ones. Based on data obtained from Scopus, 167 publications had at least three citations. The authors of the respective publications are listed in Bibliographic coupling connects two papers that have another paper in common . This rePoultry Science, with 14 co-citations and a total link strength of 94. In that paper, researchers measured the effects of in ovo feeding with highly digestible carbohydrates and β-hydroxy-β-methylbutyrate.References with at least three citations were selected for co-citation analysis. In the analysis, seven clusters were formed  and the Of 914 authors, 182 had at least two documents, but only 57 with links. The authors were grouped (represented by the colors of lines and circles) into nine clusters A. ResearA total of 914 authors were identified. By limiting the numbers to four citations and four documents per author, 28 authors were included in the citation network A. HighesAuthors who had at least 20 citations from 242 publications underwent co-citation analysis. Based on the results of the analysis, the authors were grouped into seven clusters ; the mosAll keywords with at least three occurrences were selected. Of a total of 558 keywords co-occurrence, 70 meet the threshold, 46 with links. Keywords used in the search have been removed. Keywords with the same meaning were merged. Broiler (36 occurrences), performance and growth performance , and immunity (14 occurrences) were the most prominent terms, showing strong correlation. They present the largest circles and are close together A. These ® to identify which journals globally publish and disseminate the most research on the in ovo injection technique with an emphasis on hatchability. Only 16 met this condition, as shown in Poultry Science (impact factor 4.014) is the most cited journal and has the greatest bibliographic coupling strength  , which publishes papers in areas such as animal physiology, animal nutrition, and feeding technology, Animals (impact factor 3.231), which publishes papers in any field of study involving animals, and Animal (impact factor 3.73), which publishes cutting-edge papers related to animals (farmed or managed). Animals was the journal that published the most articles on the subject and has recently been the most cited  . This jost cited .Poultry Science (2045 citations). Once again it demonstrated its capacity for contributing, sharing, and disseminating high quality work. In this regard, it appears that Poultry Science, as a specific and relevant poultry journal, is of most interest to researchers in this field.Journals with at least 23 citations were included in the co-citation analysis. Of the 3560 total citations, 34 journals met this criterion. Two large groups were formed , and theThe publications were prepared by researchers from 33 countries . To analTo evaluate the effects of in ovo injection on hatchability, studies were selected (n = 86) from the past two decades (2002–2022) that included hatchability (keyword used as a filter to aid in the selection of papers) as an evaluative parameter of substances applied in ovo . ImproviBased on the studies reviewed , solutioThe concentration and volume determine the effects of the injected substance on avian survival, directly influencing the hatchability rate. Thus, these are important factors for determining conflicting hatch rates. Gao et al.  demonstrResearchers need to redesign protocols for injecting substances in ovo that have adverse side effects due to the concentration and volume of the solution. Prior knowledge of the substance’s toxicity is necessary to achieve the optimal concentration and volume more quickly, or to discard the substance immediately if it is toxic at the minimum effective concentration. This review shows that the practice of in ovo injection performed in either the prenatal or perinatal stages of embryonic development, using safe and efficient products, can improve hatchability. However, in most cases, despite improving the health parameters of the poultry, the products were not efficient enough to influence hatchability. In a minority of cases, worsening of hatchability was reported. These results are largely dependent on the intrinsic factors of the practice. Because the products are injected directly into the embryonic environment, the health parameters of poultry appear always to undergo positive or negative changes, even if these are minimal or not significant. The positive effects stand out and many are similar between the different products tested, suggesting that they act on deficient targets common in avian organisms.Poultry Science. It can be seen that in the last 12 years, research on the subject has taken a great step forward due to the interest that the poultry sector has in practices that can strengthen and leverage its production systems. It is hoped that this review will help researchers pave the way for establishing and validating protocols that are feasible for official inclusion in commercial poultry practices. The difficulty in standardizing between studies the stages of the in ovo application protocol (regardless of the substance applied) is a barrier that can be overcome with the development of field research supervised by a collaborative network involving different countries, researchers, research centers, and the poultry sector.This review provides a broad overview of just over 38 years’ research on the subject, revealing that studies significantly increased and peaked in 2020, were produced primarily by US researchers, and were published primarily in the renowned journal This review also reveals that despite some negative reports relating to substances in the embryo, in ovo delivery of substances has the potential to change the poultry industry for the better in terms of production rates (hatchability) and/or poultry health. To make this technology applicable to the poultry industry there is a demand for active, efficient, safe, reliable, and cheap substances. These need to be tested at laboratory and industrial levels. Future studies must focus on elucidating the main embryonic physiological targets of substances delivered in ovo that are most likely to improve hatchability.