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IntroductionThis study investigated the quality of sleep in a sample of individuals from Southern Italy after the major waves of the COVID-19 pandemic, with the aim of evaluating how sleep patterns changed.MethodsA cross-sectional study was conducted between March 2022 and January 2023 and involved adults who had a COVID-19 infection, who were invited to complete a self-administered online questionnaire.ResultsA total of 408 individuals participated in the survey. Overall, 66.4% had a reduction in social relations; 72.1% had an increase in the use of social media; and 86%, 77.2%, and 71.1% reported an extremely severe level of anxiety, stress, and depression, respectively. Almost all of the respondents had a Pittsburgh Sleep Quality Index score (PSQI) ≥5, indicating poor sleep quality. Subjects with a severe or extremely severe depression score, a severe or extremely severe stress score, who had a job, and who had someone close who died because of a COVID-19 infection were more likely to have a high PSQI global score. The use of sleep medication in the past months was significantly higher in those who were older, who had a job, who had a COVID-19 infection in the first and second waves, who had someone close who died from COVID-19, and who did not have changes in social relationships during the pandemic. Moreover, participants with severe or extremely severe depression scores, with severe or extremely severe stress scores, who were women, and who were older had troubles staying awake while engaging in social activities during the past month.ConclusionThe results bring to light the high prevalence of poor sleep quality among individuals who were infected with SARS-CoV-2. Future research is needed to understand whether these disturbances are still present in the endemic period and whether it is necessary to investigate further determinants that have affected and/or are affecting sleep quality.

IntroductionAnnual influenza and COVID-19 vaccinations are effective tools for reducing the disease burden. The goals of the present cross-sectional survey were to investigate attitudes and behaviors toward the simultaneous vaccination against seasonal influenza and COVID-19 and the factors associated.MethodsQuestionnaires were self-administered or researcher-administered between October 2023 and February 2024 in an immunization center in the southern part of Italy.ResultsAll 151 subjects eligible for influenza and COVID-19 vaccinations who attended the center agreed to participate. A total of 59.9% of respondents received concurrent seasonal influenza and COVID-19 vaccinations. Those who perceived that the simultaneous vaccination was safer and those who have been infected by SARS-CoV-2 fewer times were more likely to have simultaneously received both vaccinations. Regarding the reasons reported, half of the sample stated that the simultaneous vaccination was safe and that they were adequately informed. This was more likely indicated by the respondents who had received at least four doses of the COVID-19 vaccination. Among those who had not received the simultaneous vaccination, 70.7% and 29.3% had received only seasonal influenza and COVID-19.ConclusionEducational health communication campaigns are necessary to improve compliance with simultaneous administration of seasonal influenza and COVID-19 vaccinations and to increase the unsatisfactory coverage.

Background: To tackle future health threats, the study aimed to assess healthcare workers’ (HCWs) adherence to infection prevention and control (IPC) measures and to evaluate whether knowledge and concerns related to COVID-19 could be its potential predictors. A secondary aim was to explore how and how much healthcare facilities support HCWs to implement IPC practices. Methods: This cross-sectional study was conducted between June and September 2021 in Southern Italy using a self-administered questionnaire. Socio-demographic and professional characteristics, COVID-19 preparedness and response plan in the facilities, knowledge about COVID-19’s transmission and non-pharmaceutical interventions (NPIs), concerns about the possibility of transmitting COVID-19 to family members and patients, adherence to IPC practices, and sources of information were investigated. Results: Among the 492 enrolled HCWs, the overall knowledge median score was 6 out of a maximum score of 8 and predictors of good knowledge were practicing in a facility that organized training courses about IPC measures and having more years in practice. HCWs were more concerned about the possibility of transmitting the infection to their family members (64.4%) than to negative patients (38.9%). A sizable proportion claimed to take off the face mask by touching only the straps or ties (76.3%) and to replace the face mask when it was wet (70.7%). Only 26.2% never/rarely touched the face mask while wearing it. Good adherence to preventative practices was more likely in HCWs other than physicians and practicing in a facility that organized training courses about IPC measures and in regional hospitals compared with those practicing in district hospitals. Conclusions: The study findings produce information about what worked well and where gaps were identified during COVID-19 pandemic, along with data useful for hospitals and health systems in general to better prepare and put in place appropriate interventions in case of similar future events.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum samples were collected from 83 patients infected by SARS-CoV-2 during the two first waves of COVID-19, before the availability of SARS-CoV-2 vaccination. Samples were collected at enrollment, day 11, and day 28; and patients had differing severity of disease. In this comprehensive study, we measured cell-free DNA, neutrophil activation, deoxyribonuclease I activity, complement activation, and D-dimers in longitudinal samples of COVID-19 patients. We show that all the above markers, except deoxyribonuclease I activity, increased with disease severity. Moreover, we provide evidence that in severe disease there is continued neutrophil and complement activation, as well as D-dimer formation and nucleosome release, whereas in mild and moderate disease all these markers decrease over time. These findings suggest that neutrophil and complement activation are important drivers of microvascular complications and that they reflect immunothrombosis in these patients. Neutrophil activation, complement activation, cell-free DNA, and D-dimer levels have the potential to serve as reliable biomarkers for disease severity and fatality in COVID-19. They might also serve as suitable markers with which to monitor the efficacy of therapeutic interventions in COVID-19.

Background: The purpose of this study was to evaluate the knowledge, attitude, and current practices about prevention of meningococcal disease among general practitioners (GPs) and primary care pediatricians (PCPs) in Italy. Methods: A cross-sectional survey was carried out between February 2022 and July 2023 among a random sample of GPs and PCPs in Southern Italy. The data were collected using a questionnaire accessible via an internet link with the free software Google Forms®. Results: Regarding the participants’ knowledge toward meningococcal vaccinations, 84.2% of the PCPs and more than half of the GPs (55.2%) knew that the meningococcal B (MenB) vaccination is recommended for infants from the second month of life and 84.2% and 82.7% of the PCPs were aware that quadrivalent meningococcal ACWY (MenACWY) vaccine is recommended for children in the second year of life and adolescents, respectively. The GPs and PCPs considered vaccination against meningococcal disease to be very effective and safe with average values of 8.8 and 8.7, respectively, on a scale ranging from 1 to 10. Those with an older age, those who knew the medical conditions that expose patients to a higher risk of contracting meningococcal disease, and those who self-rated their knowledge on meningococcal disease as excellent/very good were more likely to consider the vaccination to be very effective and safe. Only 15.5% of the GPs and more than half of the PCPs (54.3%) administered anti-meningococcal vaccines to their patients. GPs and females were less likely to administer anti-meningococcal vaccines to their patients, whereas those who acquired information on meningococcal vaccinations by scientific journals were more likely to administer meningococcal vaccines. Conclusions: The findings of the survey highlighted the need of a greater engagement of GPs and PCPs in the immunization campaigns in order to increase meningococcal vaccination coverage.

Background: This cross-sectional survey aimed to explore the reasons for receiving the HPV vaccination among eligible adults in Italy. Methods: The survey was conducted from July 2023 to April 2024 in Naples, Southern Italy. Results: A total of 282 questionnaires were collected. The majority of the respondents (73.2%) was aware that HPV vaccination was recommended and this was more likely among women, healthcare workers (HCWs) or students in health sciences, and those who had acquired information from physicians. The most frequently cited reasons for vaccinating were self-protection from the infection (77.6%) and from cervical/oral/penile/anal cancer (68.9%), knowing that the vaccination was free of charge (46.2%), awareness of the severity of the HPV disease (43%), to protect their partner (42.6%), and perception of being at risk (24.2%). Being HCWs or students in health sciences, believing that HPV infection could cause a serious disease, and having a higher number of oral intercourse experiences in the last year were significant predictors of the perception of being at risk. Female and Italian respondents were more likely to receive the HPV vaccination because it was effective in preventing cancer. Conclusions: Targeted educational programs and health interventions should be developed to ensure enhancing knowledge and fostering positive attitudes toward the HPV vaccination.

IntroductionDuring the COVID-19 pandemic, adherence to wearing face mask and washing hands procedures and achieving high COVID-19 vaccine coverage among healthcare workers (HCWs) were essential to minimize morbidity and possible death and limit the transmission of the virus. The objectives of the cross-sectional survey were to explore the influence of COVID-19 on the use of preventive measures and vaccination willingness among HCWs in the southern part of Italy and the associated factors.MethodsThe survey was carried out from 15 June 2023 to 15 July 2023 among 521 HCWs who worked in three randomly selected public hospitals. All data were collected through a self-administered questionnaire.ResultsHCWs had a positive change in the use of preventive measures if they did not often/always use them before the pandemic, but they are using in the current epidemiologic context and they were willing to use in a future epidemic situation. A positive change in the adherence to face mask-wearing (24.6%) was more likely among those with at least 5 years of university degree, nurses/midwives, and who had worked in COVID-19 wards. A positive change in alcohol-based hand rubbing (3.1%) was more likely in HCWs in Emergency/Critical/Infectious Diseases wards compared with medical wards. HCWs who were more likely to believe that the COVID-19 vaccine should be mandatory for them (58.1%) had at least 5 years of university degree, in Emergency/Critical/Infectious Diseases wards compared with surgical and medical wards, had received more than three doses of this vaccine, were more concerned to get infected during their activity, and had received information from scientific journals. HCWs more willing to receive the COVID-19 vaccine every year (39.8%) were males, physicians, those in Emergency/Critical/Infectious Diseases wards compared with medical wards, who had received more than three doses of this vaccine, who believed that this vaccine should be mandatory for HCWs, and who needed additional information.DiscussionThe survey showed that the COVID-19 pandemic had an impact on the use of preventive measures among HCWs, not necessarily for the improvement or increase. Educational messages on the importance of these measures regarding the promotion and recommendation of the vaccine need to be investigated and applied among HCWs in order to reduce vaccination gaps and the spread of the infection.

IntroductionThis study explored the quality of sleep among university students in the South of Italy during the Covid-19 pandemic.MethodsA cross-sectional study was conducted between March 2022 and January 2023 and involved students over the age of 18, who were invited to complete a self-administered questionnaire using an online application.ResultsOverall, 88% of men and 94.5% of women had Pittsburgh Sleep Quality Index (PSQI) scores of ≥5 and a mean PSQI score of 9.2 ± 3. Students with severe or extremely depression score, with sever or extremely stress score, male and who did not had Covid-19 infection were more likely to have a PSQI global score. Moreover, 62.6% of the students declared a reduction in social relations and 72.3% an increase in the use of social media during the pandemic period. The majority of respondents reported an extremely severe level of depression (68.1%), anxiety (84.4%) and stress (71.9%).ConclusionThis finding indicate that a relevant percentage of students are poor sleepers with a higher overall PSQI score with depression and stress and underline the role the implementation of public health interventions to promote healthy life styles and in particular focus on the duration of long night sleep.

Background and objectiveTreatments of lymphoma can lead to reduced physical functioning, cancer-related fatigue, depression, anxiety, and insomnia. These side effects can negatively impact the cancer survivor's quality of life. Mounting evidence indicates that physical activities are highly therapeutic in mitigating the short- and long-term side effects of cancer treatments. Yet, lymphoma survivors' participation in physical activities remains suboptimal, which has been further exacerbated by the deleterious effects of isolation during the COVID-19 pandemic. The Lymfit intervention aims to offer motivational support, expert guidance, and a personalized exercise prescription to optimize physical activities among lymphoma survivors. This proof-of-concept study explores implementation feasibility (retention, technical and safety), and the preliminary effects of Lymfit on various health outcomes.MethodThis was a single-armed trial with a pre-and post-test design. Twenty lymphoma survivors were recruited to participate in the 12-week Lymfit intervention. Wearable activity trackers (Fitbit) were given to participants as a motivational tool and for data collection purposes. Participants received a personalized exercise prescription designed by a kinesiologist. Physiologic metrics were collected by the Fitbit monitors and were stored in the Lymfit database. Self-reported questionnaires measuring health outcomes were collected at baseline and post-intervention.ResultsThe retention rate of this trial was 70%. Minimal technical issues and no adverse effects were reported. Lymfit led to significant improvements in sleep disturbances and the ability to participate in social activities and decreased fear of cancer recurrence. It also increased daily steps and decreased sedentary time in participants who did not meet the recommended physical activity guidelines.SignificanceWith access to resources and fitness centers being limited during the pandemic, the Lymfit intervention filled an immediate need to provide physical activity guidance to lymphoma survivors. Findings provide preliminary support that implementing the Lymfit intervention is feasible and demonstrated promising results.

Background: The aims of the study were to determine, in the urine and oral samples of young adults, the genotype-specific prevalence of Human Papilloma Virus (HPV) infection, the HPV DNA type-specific prevalence in unvaccinated and vaccinated individuals, and the determinants of HPV infection. Methods: Selected participants were asked to fill in a self-administered questionnaire and to self-collect urine and saliva samples. Results: Among the 1002 participants, 81 (8.1%) resulted positive for HPV DNA. The most common low-risk genotype was HPV 42 (2.2%), followed by HPV 43 (0.8%), and 40 (0.5%). The HPV 51 was the most common high-risk genotype (1.5%) followed by HPV 66 (1%) and HPV 68 (1%), and no participants were infected with HPV genotypes 18, 33, 45. Females, those who have had one or more occasional sexual partner, those who never/rarely/sometimes used condoms during their sexual activity, those with a previous diagnosis of sexually transmitted infection, and those who were not vaccinated were more likely to be tested positive for HPV infection. Conclusions: The low prevalence of genital HPV infections has provided evidence of the effectiveness of HPV vaccination both in vaccinated and not yet vaccinated subjects through herd immunity and indicated its decisive role in the changing epidemiology of circulating HPV genotypes in the population.

Background: This study was conducted to assess parents’ willingness to vaccinate their children with the RSV vaccine and the key predictors of this intention among parents in Italy. Methods: Data were collected using an anonymous self-administered questionnaire from April to November 2023, targeting parents in public kindergartens and nursery schools in southern Italy. The survey assessed parents’ socio-demographic characteristics, health-related details, their child’s health status, attitudes toward RSV infection and its vaccine, and their source(s) of information. Results: A total of 404 parents agreed to participate in the study. Only 18.2% of participants were very concerned that their children could get infected by RSV, and this concern was more likely among parents whose child had been diagnosed with bronchiolitis, those who received information from HCWs, those who had heard of RSV, and those who needed additional information. Almost half (51.3%) were willing to vaccinate their child, and this inclination was more likely among fathers, employed parents, those with daughters, those who had heard of RSV, those who received information from HCWs, and those who needed additional information. Conclusions: An educational campaign regarding a future RSV vaccine, especially about its safety and efficacy, is needed in order to improve parents’ willingness.

Background: This cross-sectional survey investigated the knowledge, attitudes, and coverage of recommended vaccinations among a random sample of patients with chronic medical conditions, at higher risk of vaccine-preventable diseases (VPDs), in Italy. Methods: The survey was conducted via telephone-based interviews. Results: Multinomial regression analysis showed that the patients who believed that VPDs were severe were more likely to know one recommended vaccination; those who believed that VPDs were severe and those who were advised from a general practitioner (GP) were more likely to know two vaccinations; those who were older, graduated, with more time from diagnosis, who believed that VPDs were severe, who did not need additional information, and who were advised from a GP were more likely to know three or four vaccinations. Patients who knew at least one vaccination, who perceived themselves at risk, and who were advised from a GP were more likely to have received one vaccination; those who knew more than one vaccination and who were advised from a GP were more likely to receive two or three vaccinations. Among the unvaccinated, patients who were unmarried/not cohabiting, those who needed information, and who believed that vaccinations were useful and safe were more willing to receive the recommended vaccinations. Conclusions: Educational interventions are needed to improve the adherence of individuals with chronic medical conditions.

IntroductionIn Italy, since December 2022, the COVID-19 vaccination has been extended to children aged 6 months–4 years with conditions of fragility and to those healthy at the request of the parent. The purposes of the cross-sectional survey were to determine the willingness and hesitancy of the parents/guardians to have their healthy children vaccinated against COVID-19.MethodsThe survey was performed among 389 parents/guardians with a child aged 6 months–4 years randomly selected from seven kindergartens and eight nursery schools in the geographic area of Naples, Italy.ResultsOnly 10.5% were very concerned about the risk of infection, and the mean values regarding the perceived utility and safety of the COVID-19 vaccine were 3.3 and 3.2, respectively. Only 13.7% of participants were willing to consent to vaccinate the selected child against COVID-19, while 20.1% were uncertain and 66.2% did not intend. Parents/guardians of older children, those who received information about the COVID-19 vaccine from physicians or pediatricians, those who believed that the COVID-19 vaccine was useful, and those with lower hesitancy regarding the COVID-19 vaccine were more willing to vaccinate their child. The mean Parent Attitudes About Childhood Vaccines (PACV-5) score was 5.6, with 33.1% of respondents who were identified as highly hesitant toward COVID-19 vaccination (score ≥ 7). Parents/guardians with a lower perceived safety of the COVID-19 vaccine were more likely to be highly hesitant.DiscussionThe findings reveal the need to improve community-based education campaigns and effective promotion of the COVID-19 vaccination to increase willingness and address parental safety concerns.

Abstract In Covid-19, anticoagulation with heparin is often administered to prevent or treat thromboembolic events. Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin treatment, caused by heparin-dependent, platelet activating anti-platelet factor 4 (PF4)/heparin antibodies. Diagnosis of HIT is based on the combination of clinical parameters, allowing to determine the pretest probability, and laboratory testing for anti-PF4/heparin antibodies and confirmatory functional assays, such as the heparin-induced platelet activation (HIPA) test. We report the case of a patient with severe Covid-19 pneumonia requiring ECMO treatment, who developed recurrent clotting of the ECMO filter and a drop in platelet count under heparin treatment. He was therefore suspected to have HIT and the anticoagulation was switched to argatroban. Despite high clinical probability and high titres of anti-PF4/heparin antibodies, the functional HIPA test was negative. Nevertheless, argatroban was continued rather than to reinstate anticoagulation with heparin. Reevaluation 7 days later then demonstrated a strongly positive functional HIPA test and confirmed the diagnosis of HIT. Under anticoagulation with argatroban the patient gradually improved and was finally weaned off the ECMO. In conclusion, this case highlights the critical importance of clinical judgement, exploiting the 4 T score, given that Covid-19 patients may present a different pattern of routine laboratory test results in HIT diagnostics. The possibility of a false negative HIPA test has to be considered, particularly in early phases of presentation. In cases of a discrepancy with high clinical probability of HIT and/or high titre anti-PF4/heparin antibodies despite a negative HIPA test, a reevaluation within 3 to 5 days after the initial test should be considered in order to avoid precipitant reestablishment of unfractionated heparin, with potentially fatal consequences.

Background: This survey investigated the knowledge, attitudes, and behaviors towards HPV preventive measures among university students in Italy and their associated factors. Methods: The cross-sectional survey was conducted between November 2022 and April 2023. Results: Only 41.7% knew about HPV infection and the main preventive measures. Multilevel mixed-effects logistic regression analysis showed that females, those aged 25–30 years, those who have had oral sex, those who had received information about HPV infection and preventive measures from physicians, and those who needed additional information about HPV infection and preventive measures were more knowledgeable. Only 39.1% have received at least one HPV vaccination dose, whereas 29.2% and 31.7% had not been vaccinated or did not remember. Multilevel mixed-effects logistic regression analysis identified that female students enrolled in the field of health sciences, those who did not report a prior history of a sexually transmitted infection, and those with a higher knowledge about HPV infection and preventive measures were more willing to receive the HPV vaccination. Conclusions: Despite some limitations, this was the first detailed survey on this topic conducted in the post-acute phase of COVID-19 among university students in Italy. The survey underlined the need to develop and to implement comprehensive educational programs and health interventions among students, to enhance their knowledge and modify their attitudes and improve the HPV vaccine uptake.

Background: The Post-COVID syndrome, characterized by persistence of psychological, neurologic, and physical symptoms, affects a large proportion of COVID-19 survivors. Specifically, females seem at increased risk of experiencing more psychological manifestations of Post-COVID Syndrome. Methods: A sample of 60 PCR (Polymerase Chain Reaction) confirmed COVID-19 outpatients (48.3% female; age mean= 56.1; SD= 10.8) attending an outpatient clinic dedicated to Post-COVID-19 follow-up was enrolled for this study. Each participant completed the Psychosocial Index to assess stress, well-being, psychological distress, and illness behavior, the Impact of Event Scale – Revised to evaluate post-traumatic stress symptoms and, the Hospital Anxiety and Depression Scale to assess anxiety and depression; the Connor-Davidson Resilience Scale to assess resilience; and N scale of NEO Five Factor to assess “Neuroticism”. Results: More than half of patients showed clinical or subclinical anxiety and depressive symptoms. Post-traumatic stress symptoms were found in 58.3% of sample. Resilience levels were in a medium range (71.0 ± 15.2). Statistical analysis found a predominance of depressive symptomatology (p = 0.0453), hyperarousal manifestations (p = 0.0049), perception of stress (p = 0.0001) and trait of neuroticism in women (p 0.0001). Our results show psychological distress, post-traumatic symptoms, poor psychological well-being, depression and anxiety symptoms for several weeks after infection in patients who had COVID-19. Moreover, female outpatients had a higher perception of distress, hyperarousal manifestations and depressive symptomatology than the male counterpart. Conclusions: As a novelty, this study gives us a deeper understanding of the psychological Post-COVID-19 profile in a clinical sample of pneumological outpatients. Moreover, it focused on gender differences identifying the female gender as a risk factor with respect to psychological illness. Our findings suggest the relevance of planning personalized interventions and assessment aimed at higher psychopathological risk groups, such as females.

Anticoagulants are essential in preventing and treating thrombosis. Unfortunately, their use is accompanied by an enhanced risk of bleeding. Since the introduction of direct oral anticoagulants (DOACs), the risk of major bleeding has been reduced but not eliminated. Major bleeding events related to the use of factor Xa inhibitors can be challenging to manage. In recent years, four-factor prothrombin complex concentrates have been used in patients with severe bleeding taking oral direct factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). Andexanet alfa (OndexxyaTM, AstraZeneca AG) is a specially designed recombinant version of human factor Xa that acts as a decoy receptor to reverse the effects of factor Xa inhibitors. Since 2 December 2020, andexanet alfa has been used in Switzerland for adult patients receiving apixaban or rivaroxaban when reversal of anticoagulation is required because of life-threatening or uncontrolled bleeding. However, the use of andexanet alfa remains a challenge owing to its cost, the reported thrombotic complications and the fact that its efficacy mainly relates to intracranial haemorrhage. Moreover, the use of nonspecific reversal agents together with andexanet alfa is controversial. The present recommendations on the use of andexanet alfa in the management of bleeding in patients on factor Xa inhibitors in Switzerland were developed by a group of Swiss experts from the Working Party Hemostasis of the Swiss Society of Hematology. These recommendations aim to provide support to clinicians in their decision-making in the management of patients with major bleeding receiving factor Xa inhibitors.

BackgroundIn Italy, on December 2022, COVID-19 vaccination was recommended for children aged 6 months-4 years with frail conditions and for those healthy. The purposes of the survey were to understand parental willingness and hesitancy toward COVID-19 vaccination of children with frail conditions in Italy and related influencing factors.MethodsA cross-sectional survey was performed among 445 parents with a child aged 6 months-4 years with frail conditions who attended a teaching hospital and a public hospital randomly selected in the city of Naples, Italy.ResultsAlmost one third (29.9%) were willing to vaccinate their frail children against COVID-19, whereas 21.3% were uncertain, and 48.8% did not intend to vaccinate. Parents with a higher level of perception that the vaccine is useful and safe and those who had received information by pediatrician were more likely to be willing to vaccinate their child. The mean Parent Attitudes About Childhood Vaccines (PACV-5) score was 3.4, with 13.5% of parents high-hesitant for the COVID-19 vaccination for their child. Parents with a higher COVID-19 vaccine-related safety concerns, those who have delayed at least one shot of a recommended vaccine for their child, and those who did not have received at least three doses of the vaccine against SARS-CoV-2 were more likely to be high-hesitant.ConclusionThe survey findings have important implications for designing interventions to increase willingness and to reduce hesitancy for COVID-19 vaccine among parents of frail children aged 6 months-4 years in Italy.

Nancy Cross,1 Cécile van Steen,2 Yasmina Zegaoui,1 Andrew Satherley,1 Luigi Angelillo2 1Market Access, Lightning Health, London, UK; 2Market Access, Health Technology Assessment & Health Economics and Outcome Research, Europe, the Middle East and Africa, Santen GmbH, Munich, Bavaria, GermanyCorrespondence: Yasmina Zegaoui, Market Access, Lightning Health, 8 Devonshire Square, London, EC2M 4PL, UK, Tel +44 7770918748, Email yzegaoui@lightning.healthAbstract: Retinitis Pigmentosa (RP) is a group of inherited retinal dystrophies (IRDs) characterised by progressive vision loss. Patients with RP experience a significant impact on daily activities, social interactions, and employment, reducing their quality of life. Frequent delays in referrals and no standard treatment for most patients also contribute to the high unmet need for RP. This paper aims to describe the evolving therapeutic landscape for RP including the rationale for advanced therapy medicinal products (ATMPs). A review of available data was conducted in three stages: (1) a search of publicly available literature; (2) qualitative research with physicians treating RP patients in France, Germany, Italy, Spain, and the UK; and (3) a review of leading candidates in the RP pipeline. Globally, there are currently over 100 drugs in development for RP; 50% of which are ATMPs. Amongst the 15 cell and gene therapies in late-stage development, 5 leading candidates have been selected to profile based on the development stage, drug target and geography: gene therapies AGN-151597, GS-030 and VMCO-1 and human stem cell therapies jCell and ReN-003. Hereditary retinal diseases are suitable for treatment with cell and gene therapies due to the accessibility of the retina and its immune privilege and compartmentalisation. Therapeutic approaches that aim to rescue photoreceptors (eg gene therapies) require that non-functional target cells are still present, whereas other therapies (eg cell therapies) are not reliant on the presence of viable photoreceptors. Gene therapies may be attractive as their fundamental goal is to restore vision; however, cell therapies will likely have a broader application and do not rely on genetic testing, which can delay treatment. Ensuring effective therapeutic options for RP patients across disease stages requires the continued diversification and advancement of the development pipeline, and sustained efforts to promote early patient identification and timely diagnosis.Keywords: treatment, retinitis pigmentosa, retinal dystrophy, cell therapy, gene therapy, therapeutic landscape

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.

Nancy Cross,1 Cécile van Steen,2 Yasmina Zegaoui,1 Andrew Satherley,1 Luigi Angelillo2 1Market Access, Lightning Health, London, England, UK; 2Market Access HTA & HEOR, EMEA, Santen GmbH, Munich, Bavaria, GermanyCorrespondence: Yasmina Zegaoui, Market Access, Lightning Health, 8 Devonshire Square, London, EC2M 4PL, England, UK, Tel +447770918748, Email yzegaoui@lightning.healthAbstract: Retinitis Pigmentosa (RP), a group of inherited retinal dystrophies characterised by progressive vision loss, is the leading cause of visual disability and blindness in subjects less than 60 years old. Currently incurable, therapy is aimed at restricting degeneration of vision, treating complications, and helping patients to cope with the psychosocial impact of their disease. Hence, RP is associated with a high burden of disease. This paper describes the current therapeutic landscape for RP and the disease burden for patients, caregivers, and society. A review of available data was conducted in three stages: (1) a literature search of publicly available information on all domains of RP; (2) a systematic literature review using Medline, Embase, the Cochrane Library and grey literature (GlobalData) on epidemiology and cost of RP; and (3) qualitative research with senior physicians treating RP patients in the EU4 and the UK to validate research findings from secondary sources. RP severely impacts the daily lives of over a million people worldwide. Progressive vision loss significantly affects the ability to perform basic daily tasks, to maintain employment, and maintain independence. Consequently, most patients will experience reduced quality of life, with a greater emotional and psychological impact than other conditions related to vision loss such as diabetic retinopathy or age-related macular degeneration. RP is also associated with a high level of carer burden, arising from psychological and financial stress. The therapeutic landscape for RP is limited, with few treatment options and minimal guidance for the diagnosis, treatment, and care of patients. A curative intervention, voretigene neparvovec (Luxturna®), only exists for 1– 6% of patients. Although disease management can be successful in developing coping strategies, most patients live with this chronic, progressive condition without interventions to change the disease course. Innovative new therapies can transform the therapeutic landscape, provided appropriate clinical guidance is forthcoming.Keywords: treatment, burden of disease, retinitis pigmentosa, visual impairment, retinal dystrophy

Abstract Colorectal carcinoma is the second leading cause of cancer-related deaths, and indeed, rectal cancer accounting for approximately one third of newly diagnosed patients. Gold standard in the treatment of rectal cancer is a multimodality approach, aiming at a good control of the local disease. Distant recurrences are the major cause of mortality. Currently, Locally Advanced Rectal Cancer (LARC) patients undergo a combined treatment of chemotherapy and radiotherapy, followed by surgery. Eventually, more chemotherapy, namely adjuvant chemotherapy (aCT), may be necessary. Total Neoadjuvant Therapy (TNT) is an emerging approach aimed to reduce distant metastases and improve local control. Several ongoing studies are analyzing whether this new approach could improve oncological outcomes. Published results were encouraging, but the heterogeneity of protocols in use, makes the comparison and interpretation of data rather complex. One of the major concerns regarding TNT administration is related to its effect on larger and more advanced cancers that might not undergo similar down-staging as smaller, early-stage tumors. This minireview, based on a systematic literature search of randomized clinical trials and meta-analysis, summarizes current knowledge on TNT. The aim was to confirm or refute whether or not current practice of TNT is based on relevant evidence, to establish the quality of that evidence, and to address any uncertainty or variation in practice that may be occurring. A tentative grouping of general study characteristics, clinical features and treatments characteristics has been undertaken to evaluate if the reported studies are sufficiently homogeneous in terms of subjects involved, interventions, and outcomes to provide a meaningful idea of which patients are more likely to gain from this treatment.