The Role of Attention in Placebo and Nocebo Effects.

BACKGROUND: Although some existing models propose that attention may be crucially implicated in placebo/nocebo effects, empirical research on this aspect remains limited and scattered. PURPOSE: This systematic review aims to provide an inclusive overview of studies that have either directly manipulated or assessed attention within the context of placebo and nocebo procedures so to gain a synthetized picture of the role of this variable in placebo/nocebo effects. Importantly, only studies in which attention represented a mechanism or mediator of the placebo/nocebo response, and not a primary outcome, were included. METHODS: A systematic search was conducted across multiple databases, including PubMed, Scopus, PsycINFO, Web of Science, and Embase, to identify peer-reviewed studies. These studies were subjected to methodological evaluation and eligibility criteria for inclusion. RESULTS: We identified and classified 12 studies into three categories based on their focus: (i) those that directly assessed attention, (ii) those that directly manipulated participants' attention, and (iii) those that combined both a direct manipulation and assessment of attention. In all selected studies attention acted as a mechanism or mediator of the placebo/nocebo response, and was not considered a primary outcome of the placebo/nocebo manipulation. CONCLUSIONS: The synthesis of the included studies reveals that the role of attention in placebo and nocebo effects is still a topic of debate, marked by variations in how attention is conceptualized and measured. Results suggest that attention has significant clinical implications, particularly in optimizing therapeutic efficacy by directing patients' focus toward signs of healing and away from indicators of illness or distress. To advance our understanding, future research should explore these attentional mechanisms, in conjunction with neurophysiological correlates.

To date, empirical research on the role of attention in placebo/nocebo effects remains scarce and inconclusive. The aim of this systematic review is to offer an overview of studies that have either directly manipulated or assessed attention as a mechanism or mediator of placebo/nocebo responses. Peer-review studies were subjected to methodological evaluation and eligibility criteria, and 12 studies were selected and classified into 3 categories based on their focus: (i) those that directly assessed attention, (ii) those that directly manipulated participants' attention, and (iii) those that combined both a direct manipulation and assessment of attention. The synthesis of the included studies points to the nuanced methodological approaches to the study of the role of attention in placebo and nocebo effects, marked by variations in how this variable is conceptualized and measured. Overall, results support the idea that placebo/nocebo effects are not always a direct byproduct of expectations, with attention acting as an important factor to consider when exploring this relationship. Particularly, attention plays an important role in optimizing therapeutic efficacy by directing patients' focus toward signs of healing and away from indicators of illness or distress.

Pressure on the Health-Care System and Intensive Care Utilization During the COVID-19 Outbreak in the Lombardy Region of Italy: A Retrospective Observational Study in 43,538 Hospitalized Patients.

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21-March 13), the period of highest pressure on the health-care system (March 14-April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26-July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patients under 56 years of age had more limited changes in the probability of (OR = 0.65, 95% CI: 0.56, 0.76) and delay to (incidence rate ratio = 1.16, 95% CI: 0.95, 1.42) ICU admission and increased mortality (OR = 1.43, 95% CI: 1.00, 2.07). In the declining phase, all quantities decreased for all age groups. These patterns may suggest that limited health-care resources during the peak phase of the epidemic in Lombardy forced a shift in ICU admission criteria to prioritize patients with higher chances of survival.

Risk factors associated with severe hospital burden of COVID-19 disease in Regione Lombardia: a cohort study.

BACKGROUND: Understanding the risk factors associated with hospital burden of COVID-19 is crucial for healthcare planning for any future waves of infection. METHODS: An observational cohort study is performed, using data on all PCR-confirmed cases of COVID-19 in Regione Lombardia, Italy, during the first wave of infection from February-June 2020. A multi-state modelling approach is used to simultaneously estimate risks of progression through hospital to final outcomes of either death or discharge, by pathway (via critical care or not) and the times to final events (lengths of stay). Logistic and time-to-event regressions are used to quantify the association of patient and population characteristics with the risks of hospital outcomes and lengths of stay respectively. RESULTS: Risks of severe outcomes such as ICU admission and mortality have decreased with month of admission (for example, the odds ratio of ICU admission in June vs March is 0.247 [0.120-0.508]) and increased with age (odds ratio of ICU admission in 45-65 vs 65 + age group is 0.286 [0.201-0.406]). Care home residents aged 65 + are associated with increased risk of hospital mortality and decreased risk of ICU admission. Being a healthcare worker appears to have a protective association with mortality risk (odds ratio of ICU mortality is 0.254 [0.143-0.453] relative to non-healthcare workers) and length of stay. Lengths of stay decrease with month of admission for survivors, but do not appear to vary with month for non-survivors. CONCLUSIONS: Improvements in clinical knowledge, treatment, patient and hospital management and public health surveillance, together with the waning of the first wave after the first lockdown, are hypothesised to have contributed to the reduced risks and lengths of stay over time.

Maternal Psychological Factors and Onset of Functional Gastrointestinal Disorders in Offspring: A Prospective Study.

BACKGROUND/OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are a heterogeneous group of conditions of unclear etiology. The biopsychosocial model approach to FGIDs posits that early-life stressors may trigger a cascade of complex interactions between genetic predisposition and risk factors eventually leading to the occurrence of FGIDs. The relationship between the psychological disposition of the mother and FGIDs occurrence is poorly understood. We conducted a study to investigate if parental psychological factors may contribute to the onset of FGIDs in offspring. METHODS: We performed a prospective cohort study of parent-infant pairs who completed a battery of self-reported psychological questionnaires and a validated Rome III questionnaire for the diagnosis of infant and toddler FGIDs. The Edinburgh Postpartum Depression Scale (EPDS) was used to examine postpartum depression (PPD) symptoms; the Maternity Blues Questionnaire (MBQ) was applied to measure maternity blues severity; the Symptoms Checklist-Revised (SCL90-R) was used to assess the presence of relevant psychiatric symptoms; adult attachment style in mothers was assessed in a continuous way through the five dimensions of the Attachment Style Questionnaire (ASQ). RESULTS: Out of the 360 eligible mothers, 200 were enrolled, 113 completed the 3-month follow-up and were included in the final analysis. PPD symptoms prevalence was 20.4%, 20%, 13.2%, and 13.1% respectively at 3 days, 1 week, 1 month, and 3 months after delivery. 40.4% of mothers suffered from severe blues according to the MBQ. Relevant psychiatric symptoms (SCL90-R) were present in 7.8% and 10.9% of mothers, respectively at 1 week and 3 months after delivery. 48.7% of mothers showed a secure attachment pattern measured through the RQ. At 1-month follow-up, infant regurgitation was diagnosed in 26 (23%) of infants, infantile colic in 31 (27.4%), dyschezia in 17 (15%), and functional constipation in 9 (8%). At 3-month follow-up, FGIDs prevalence was respectively 16 (19.3%), 11 (13.3%), 4 (4.8%), and 11 (13.3%). A significant positive association between PPD symptoms starting 3 days after delivery and the presence of infantile colic on setting 1 month after birth was found (P = 0.028), as well as between PPD symptoms occurrence 7 days after delivery and infantile regurgitation beginning 1 month after birth (P = 0.042). A higher prevalence of infantile colic was found in the offspring of mothers suffering from PPD symptoms from 3 days after delivery (54.5 vs 19.8; P = 0.001). No significant association was found between FGIDs and psychiatric symptoms and maternity blues at any timepoint. On the other hand, mothers of infants with regurgitation with an onset 1 month after birth have higher insecurity score in avoidant and fearful ASQ-related attachment dimensions (respectively, P = 0.03, P = 0.042, P = 0.03). CONCLUSIONS: Maternal psychological factors might contribute to the onset of infant FGIDs in offspring. Early screening of postpartum depression symptoms and early implementation of psychological interventions within the postpartum period might promote the health of the mother-infant dyad.

Decreasing hospital burden of COVID-19 during the first wave in Regione Lombardia: an emergency measures context.

BACKGROUND: The aim of this study is to quantify the hospital burden of COVID-19 during the first wave and how it changed over calendar time; to interpret the results in light of the emergency measures introduced to manage the strain on secondary healthcare. METHODS: This is a cohort study of hospitalised confirmed cases of COVID-19 admitted from February-June 2020 and followed up till 17th July 2020, analysed using a mixture multi-state model. All hospital patients with confirmed COVID-19 disease in Regione Lombardia were involved, admitted from February-June 2020, with non-missing hospital of admission and non-missing admission date. RESULTS: The cohort consists of 40,550 patients hospitalised during the first wave. These patients had a median age of 69 (interquartile range 56-80) and were more likely to be men (60%) than women (40%). The hospital-fatality risk, averaged over all pathways through hospital, was 27.5% (95% CI 27.1-28.0%); and steadily decreased from 34.6% (32.5-36.6%) in February to 7.6% (6.3-10.6%) in June. Among surviving patients, median length of stay in hospital was 11.8 (11.6-12.3) days, compared to 8.1 (7.8-8.5) days in non-survivors. Averaged over final outcomes, median length of stay in hospital decreased from 21.4 (20.5-22.8) days in February to 5.2 (4.7-5.8) days in June. CONCLUSIONS: The hospital burden, in terms of both risks of poor outcomes and lengths of stay in hospital, has been demonstrated to have decreased over the months of the first wave, perhaps reflecting improved treatment and management of COVID-19 cases, as well as reduced burden as the first wave waned. The quantified burden allows for planning of hospital beds needed for current and future waves of SARS-CoV-2 i.

Rapid clinical improvement of atopic dermatitis in an Omalizumab treated patient.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disorder, whose symptoms and severity grossly depend on individual trigger factors. The majority of patients are satisfactorily treated with emollients together with topical and systemic therapies. However, treatment failure or long-term side effects with conventional treatment options can be a significant clinical problem. Recently, novel therapeutic approaches focus on targeting skewed immune responses providing a more effective, and less harmful approach. Among them, variable success has been reported using Omalizumab, when used in combination with classic therapies. This report describes an interesting case of severe adult onset difficult-to-treat atopic dermatitis dramatically improved in response to treatment with Omalizumab. CASE PRESENTATION: We present a case of an adult male with severe allergic atopic dermatitis, with concomitant involvement of the face, neckline, trunk and forearms and systemic symptoms such as diarrhoea with important decrease of his daily quality of life. The patient had been prescribed oral steroids in addition to anti-histamines to no avail. Due to lack of response to classic therapies, strict diet, as well as to treatment with intravenous corticosteroids, an off-label treatment with Omalizumab based on patient weight and total IgE value was proposed. Clear clinical results were observed after only a few weeks with regards to systemic symptoms, and just after 2 months of treatment in regards to skin involvement. CONCLUSIONS: In the majority of treated patients the clinical improvement of cutaneous manifestations is expected after several months of treatment, as skin manifestations are the consequence of a chronic inflammatory process. The outstanding rapid response observed in this case as well as the persistence of the clinical remission suggests that the block of the IgE pathways modulate functions of cells involved in the pathogenic mechanisms of chronic skin inflammation but also in the acute phases observed in the flare-ups of the disease.

Imagining flying increases jumping performance in volleyball players: A pilot study.

OBJECTIVE: The study aimed to examine the effect of mental imagery on sports performance. Specifically, it was tested whether imagining flying (i.e., air travel) increases jumping performance in a group of female volleyball players. METHODS: The study included 46 female young athletes (mean age = 15.23 years; standard deviation = 2.4) divided into two groups: the experimental group viewed a three-dimensional video that simulated a flying experience, while the control group watched neutral footage. The jump performance of both groups was measured before and after viewing the videos, using the Vertec Like® instrument to assess jump height. Participants were assessed for their flow disposition, mental imagery skills, and image vividness. RESULTS: Comparing pre-post jump performance scores, the experimental group showed a significant improvement over the control group, with a medium-large effect size (d = 0.634). There was no significant association between flow disposition, mental imagery skills, image vividness, and pre-post jumping performance differences (respectively: ß = -0.107, p = .484; ß = -0.008, p = .957; ß = 0.024, p = .913). CONCLUSIONS: These findings suggest that the experience of imagining flying, enhanced with an immersive video, has a positive effect on jumping performance in a one-session study with young female volleyball players. This effect does not appear to be associated with pre-existing characteristics or the vividness of the image itself.

Risk factors associated with nocebo effects: A review of reviews.

Objective: This meta-review aims to identify and categorize the risk factors that are associated with nocebo effects. The nocebo effect can exert a negative impact on treatment outcomes and have detrimental outcomes on health. Learning more about its potential predictors and risk factors is a crucial step to mitigating it. Methods: Literature review studies about the risk factors for nocebo effects were searched through five databases (PubMed, Scopus, The Cochrane Library, PsycINFO, and Embase) and through grey literature. Methodological validity and risk of bias were assessed. We conducted a thematic analysis of the results of the forty-three included reviews. Results: We identified nine categories of risk factors: prior expectations and learning; socio-demographic characteristics; personality and individual differences; neurodegenerative conditions; inflammatory conditions; communication of information and patient-physician relationship; drug characteristics; setting; and self-awareness. We also highlighted the main biochemical and neurophysiological mechanisms underlying nocebo effects. Conclusions: Nocebo effects arise from expectations of adverse symptoms, particularly when triggered by previous negative experiences. A trusting relationship with the treating physician and clear, tailored treatment instructions can act as protective factors against a nocebo effect. Clinical implications are discussed.

Caregivers of Neuromuscular Patients Living with Tracheostomy during COVID-19 Pandemic: Their Experience.

Background: During a pandemic, tracheostomy management in neuromuscular disease (NMD) patients can be complex. Methods: Using a multicentre, multiple case study approach, we sought perspectives through semi-structured interviews via hybrid quali-quantitative analysis. The qualitative analysis involved a semi-structured interview and the quantitative analysis the completion of a battery of questionnaires. Aim: To investigate the caregivers' experiences, burden and beliefs regarding tracheostomy during the Italian COVID-19 pandemic. The following instruments were administered: Connor and Davidson Resilience Scale (CD-RISC-25); Acceptance and Action Questionnaire-II (AAQ-II); State-Trait Anxiety Inventory (STAI); Langer Mindfulness Scale (LMS); Zarit Burden Interview (ZBI). Results: Fifty-three caregivers (62.3% female, mean age 52.2 (SD = 18.2)) participated in the study. The more resilient the carers, the more they were psychologically flexible (r = 0.380, p = 0.014) and able to cope adaptively with the emergency (r = 0.378, p < 0.006). Similarly, perceived control was higher the more resilient they were (r = 0.897, p < 0.001). The main emotions emerging were isolation and loneliness (15; 34.88%). The perception of tracheostomy meant that it could be seen as a lifesaver or as a condemnation. Similarly, the relationship with health professionals moves from satisfaction to a feeling of abandonment over the course of the pandemic. Conclusions: These findings offer a unique opportunity to understand the point of view of caregivers of NMD patients living with tracheotomy during the COVID-19 pandemic, when going to the hospital may have been hampered.

Do social media interventions increase vaccine uptake?

Introduction: The Italian mass COVID-19 vaccination campaign has included children aged 5-11 years as part of the target population since December 2021. One of the biggest challenges to vaccine uptake was vaccine hesitancy among parents and children's caregivers. Primary care pediatricians (PCPs), as the first point of contact between the National Health Service (NHS) and parents/caretakers, initiated various communication strategies to tackle this hesitancy. This study aims to evaluate the impact of a PCP-led social media intervention and a digital reminder service (DRS) on parental hesitancy regarding vaccinating their 5-11-year-old children against COVID-19. Methods: A prospective cohort study was designed, and the chosen target populations were parents and caretakers of children aged 5-11 years. Two PCP cohorts were recruited. The first group received a social media intervention and a DRS; while the second group did not. Both cohorts had access to traditional face-to-face and telephone-based counseling. The vaccination coverage rate in the two groups was evaluated. Results: A total of 600 children were enrolled. The exposed cohort (277 patients) received social media intervention, DRS, and counseling options (face-to-face and telephone-based), whereas the non-exposed cohort (323 patients) received only counseling options. In total, 89 patients from the exposed cohort did not receive any dose of the COVID-19 vaccine (32.5%), 165 were fully immunized (59.5%), and 23 received only one dose (8.5%). A total of 150 non-exposed patients did not receive any dose of the COVID-19 vaccine (47%), 147 were fully immunized (45.5%), and 24 only received one dose (7.4%). The difference between the two groups was statistically significant (chi square = 11.5016; p = 0.0006). Conclusion: Social media and DRS interventions had a positive impact on vaccine uptake and may be helpful in tackling vaccine hesitancy. Better-designed studies are needed to corroborate these findings.

Placebo and Nocebo Effects as Bayesian-Brain Phenomena: The Overlooked Role of Likelihood and Attention.

The Bayesian-brain framework applied to placebo responses and other mind-body interactions suggests that the effects on the body result from the interaction between priors, such as expectations and learning, and likelihood, such as somatosensorial information. Significant research in this area focuses on the role of the priors, but the relevance of the likelihood has been surprisingly overlooked. One way of manipulating the relevance of the likelihood is by paying attention to sensorial information. We suggest that attention can influence both precision and position (i.e., the relative distance from the priors) of the likelihood by focusing on specific components of the somatosensorial information. Two forms of attention seem particularly relevant in this framework: mindful attention and selective attention. Attention has the potential to be considered a "major player" in placebo/nocebo research, together with expectations and learning. In terms of application, relying on attentional strategies as "amplifiers" or "silencers" of sensorial information could lead to an active involvement of individuals in shaping their care process and health. In this contribution, we discuss the theoretical implications of these intuitions with the aim to provide a comprehensive framework that includes Bayesian brain, placebo/nocebo effects, and the role of attention in mind-body interactions.

Adherence to Mediterranean Diet and Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis.

Pancreatic cancer (PC) represents the 6th cause of cancer death. Although the aetiology of PC is not completely understood, numerous risk factors have been identified in association with this cancer, among them diet. However, little is known about the association between the Mediterranean Diet (MedDiet) and the risk of PC. For this reason, we conducted a systematic review with meta-analysis according to the PRISMA guidelines, searching on three databases (PubMed/MEDLINE, Scopus, and EMBASE). The protocol was registered in PROSPERO. Both fixed and random effect models were performed. The Effect size was reported as a hazard ratio (HR) with a 95% Confidence Interval (CI). A total of eight articles were included. The methodological quality of the included meta-analyses was high. Our results show that a higher adherence to the MedDiet is associated with a lower risk of PC [HR:0.82 (0.76-0.88) p < 0.001, based on 1,301,320 subjects]. The results were also confirmed in sensitivity and subgroups analyses (avoidance of potential overlapping effects, type of tools used to assess dietary intake and the diagnosis of PC, prevalence and incidence of PC risk, country where the studies took place, sex, and cancer site). Promoting a higher adherence to the MedDiet could be an effective approach to reduce the risk of PC.

Mediterranean Diet in Developmental Age: A Narrative Review of Current Evidences and Research Gaps.

Numerous studies in recent decades have shown that Mediterranean diet (MD) can reduce the risk of developing obesity in pediatric patients. The current narrative review summarizes recent evidence regarding the impact of MD across the different stages of child development, starting from fetal development, analyzing breastfeeding and weaning, through childhood up to adolescence, highlighting the gaps in knowledge for each age group. A literature search covering evidence published between 1 January 2000 and 1 March 2022 and concerning children only was conducted using multiple keywords and standardized terminology in PubMed database. A lack of scientific evidence about MD adherence concerns the age group undergoing weaning, thus between 6 months and one year of life. In the other age groups, adherence to MD and its beneficial effects in terms of obesity prevention has been extensively investigated, however, there are still few studies that correlate this dietary style with the incidence of non-communicable diseases. Furthermore, research on multi-intervention strategy should be implemented, especially regarding the role of education of children and families in taking up this healthy dietary style.

Trends in outcomes following COVID-19 symptom onset in Milan: a cohort study.

BACKGROUND: For people with symptomatic COVID-19, the relative risks of hospital admission, death without hospital admission and recovery without admission, and the times to those events, are not well understood. We describe how these quantities varied with individual characteristics, and through the first wave of the pandemic, in Milan, Italy. METHODS: A cohort study of 27 598 people with known COVID-19 symptom onset date in Milan, Italy, testing positive between February and June 2020 and followed up until 17 July 2020. The probabilities of different events, and the times to events, were estimated using a mixture multistate model. RESULTS: The risk of death without hospital admission was higher in March and April (for non-care home residents, 6%-8% compared with 2%-3% in other months) and substantially higher for care home residents (22%-29% in March). For all groups, the probabilities of hospitalisation decreased from February to June. The probabilities of hospitalisation also increased with age, and were higher for men, substantially lower for healthcare workers and care home residents, and higher for people with comorbidities. Times to hospitalisation and confirmed recovery also decreased throughout the first wave. Combining these results with our previously developed model for events following hospitalisation, the overall symptomatic case fatality risk was 15.8% (15.4%-16.2%). CONCLUSIONS: The highest risks of death before hospital admission coincided with periods of severe burden on the healthcare system in Lombardy. Outcomes for care home residents were particularly poor. Outcomes improved as the first wave waned, community healthcare resources were reinforced and testing became more widely available.

A comparative study between the incidence and epidemiological features of Influenza-Like Illness and laboratory-confirmed COVID-19 cases in the Italian epicenter (Lombardy).

INTRODUCTION: In Lombardy, the influenza surveillance system relies on sentinel physicians that weekly report data on the number of Influenza-Like Illness (ILI) and a part of them also collect nasopharyngeal samples for virologic analyses. This study aims at comparing the ILI incidence of 2019-2020 influenza season with the incidence of COVID-19 cases in order to better understand the current epidemic and to evaluate whether the implementation of ILI surveillance system could succeed in early detection and monitoring of COVID-19 diffusion. METHODS: The distribution of ILI cases in the seasons 2017-2018, 2018-2019 and 2019-2020 was taken in consideration and the curve trends were compared and analyzed according to geographical areas, age groups and time differences. RESULTS: The curve trends presented a similar pattern up to the 9th week; in fact, a reduction in the ILI incidence rate was observed in the 2017-2018 and 2018-2019 season but in the 2019-2020 an increase in the reported ILI emerged. The relation between the numbers reported by 2019-2020 ILI surveillance and those reported for COVID-19 is supported by the curve trends, the correspondence between age groups, the correspondence by geographical location, and also by the results of the nasopharyngeal swab tests performed. DISCUSSION: The influenza surveillance system is an effective tool for early detection of COVID-19. It may provide timely and high-quality data evaluating the SARS-CoV-2 burden among population with ILI. Implementation of the system has to be prioritized in order to identify any future novel respiratory pathogen with pandemic potential.

Influenza Vaccination Campaign during the COVID-19 Pandemic: The Experience of a Research and Teaching Hospital in Milan.

BACKGROUND: During the COVID-19 pandemic, more than ever, optimal influenza vaccination coverage among healthcare workers (HCWs) is crucial to avoid absenteeism and disruption of health services, as well as in-hospital influenza outbreaks. The aim of this study is to analyze the 2020 influenza vaccination campaign, comparing it with the previous year's in a research and teaching hospital in Northern Italy. METHODS: adopting an approach based on combined strategies, three interventions were deployed: a promotional and educational campaign, vaccination delivery through both ad hoc and on-site ambulatories, and a gaming strategy. Personal data and professional categories were collected and analyzed using univariate logistic regression. Vaccinated HCWs were asked to fill in a questionnaire to describe their reasons for vaccination adherence. RESULTS: the vaccination coverage rate (VCR) was 43.1%, compared to 21.5% in 2019. The highest increase was registered among administrative staff (308.3%), while physicians represent the most vaccinated category (n = 600). Moreover, residents (prevalence ratio (PR): 1.12; 95% CI 1.04-1.20), as well as intensive care (PR: 1.44; 95% CI: 1.24-1.69) and newborn workers (PR: 1.41; 95% CI: 1.20-1.65) were, respectively, the categories most frequently vaccinated for the first time. CONCLUSION: the significant increase in vaccination coverage rate confirms the suitability of the combined strategy of delivering the flu vaccination campaign and represents a first step towards reaching WHO recommended vaccination rates.

In-hospital and web-based intervention to counteract vaccine hesitancy in very preterm infants' families: a NICU experience.

BACKGROUND: Vaccine hesitancy is a global problem, carrying significant health risks for extremely vulnerable population as that of preterm infants. Social media are emerging as significant tools for public health promotion. Our aim was to evaluate both the coverage and the timeliness of routine immunizations in a cohort of preterm infants (< 33 weeks of gestational age) at 24 months of age whose families have been subjected to in-hospital and web-based interventions to counteract vaccine hesitancy. METHODS: For a period of 2 years parents of preterm infants were instructed during their follow up visits by a member of the NICU team to get correct informations about vaccines from a social network page. Vaccination rates of preterm infants were assessed at 24 months of chronological age with an electronic database and compared to both general population and historical cohort. RESULTS: Coverage and timeliness of vaccinations at 24 months of age of 170 preterm infants were analyzed in December 2019. Gestational age and birth weight median (IQR) were, respectively, 31.0 (5.0) weeks and 1475.0 (843.8) g. Coverage rates were similar to those of the regional population (p > 0.05), while timeliness of administration was significantly delayed compared to the recommended schedule (p < 0.001). Age of administration was not correlated with either body weight and gestational age at birth (Spearman rank, p > 0.05). DTaP-IPV-HBV-Hib 2nd and 3rd doses, MMR and Varicella vaccines coverage data were higher compared to historical cohort (p < 0.05). CONCLUSION: Increasing vaccine confidence through web-based interventions could have a positive impact on vaccination acceptance of parents of preterm infants, although timeliness results still delayed. There is a strong need to develop different and effective vaccination strategies to protect this very vulnerable population.

Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy.

Importance: Solid estimates of the risk of developing symptoms and of progressing to critical disease in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are key to interpreting coronavirus disease 2019 (COVID-19) dynamics, identifying the settings and the segments of the population where transmission is more likely to remain undetected, and defining effective control strategies. Objective: To estimate the association of age with the likelihood of developing symptoms and the association of age with the likelihood of progressing to critical illness after SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study analyzed quarantined case contacts, identified between February 20 and April 16, 2020, in the Lombardy region of Italy. Contacts were monitored daily for symptoms and tested for SARS-CoV-2 infection, by either real-time reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs or retrospectively via IgG serological assays. Close contacts of individuals with laboratory-confirmed COVID-19 were selected as those belonging to clusters (ie, groups of contacts associated with an index case) where all individuals were followed up for symptoms and tested for SARS-CoV-2 infection. Data were analyzed from February to June 2020. Exposure: Close contact with individuals with confirmed COVID-19 cases as identified by contact tracing operations. Main Outcomes and Measures: Age-specific estimates of the risk of developing respiratory symptoms or fever greater than or equal to 37.5 °C and of experiencing critical disease (defined as requiring intensive care or resulting in death) in SARS-CoV-2-infected case contacts. Results: In total, 5484 case contacts (median [interquartile range] age, 50 [30-61] years; 3086 female contacts [56.3%]) were analyzed, 2824 of whom (51.5%) tested positive for SARS-CoV-2 (median [interquartile range] age, 53 [34-64] years; 1604 female contacts [56.8%]). The proportion of infected persons who developed symptoms ranged from 18.1% (95% CI, 13.9%-22.9%) among participants younger than 20 years to 64.6% (95% CI, 56.6%-72.0%) for those aged 80 years or older. Most infected contacts (1948 of 2824 individuals [69.0%]) did not develop respiratory symptoms or fever greater than or equal to 37.5 °C. Only 26.1% (95% CI, 24.1%-28.2%) of infected individuals younger than 60 years developed respiratory symptoms or fever greater than or equal to 37.5 °C; among infected participants older than 60 years, 6.6% (95% CI, 5.1%-8.3%) developed critical disease. Female patients were 52.7% (95% CI, 24.4%-70.7%) less likely than male patients to develop critical disease after SARS-CoV-2 infection. Conclusions and Relevance: In this Italian cohort study of close contacts of patients with confirmed SARS-CoV-2 infection, more than one-half of individuals tested positive for the virus. However, most infected individuals did not develop respiratory symptoms or fever. The low proportion of children and young adults who developed symptoms highlights the possible challenges in readily identifying SARS-CoV-2 infections.

T Cell Response to Infliximab in Exposed Patients: A Longitudinal Analysis.

This study aimed to evaluate the proportion of infliximab (IFX)-exposed patients exhibiting cellular response to the drug in a longitudinal way and to establish whether it is predictive for anti-drug antibodies (ADA) development. Seventeen patients suffering from immuno-mediated disorders were enrolled. Blood was sampled at baseline and before each of the first eight infusions of IFX. The proliferation of PBMCs to 15-mer peptides covering VH/VL frames of IFX was assessed as well as transcription factors and cytokines mRNA expression of memory T cells in IFX-stimulated PBMCs. The number of peptides recognized by T cells after four infusions was higher than those recognized by the same patients before treatment. IFX-stimulated PBMCs from more than 90% of patients were able to express the main regulators and adaptive cytokines of memory T cells. While IFN-γ mRNAs increased after the first infusion and declined during the subsequent ones, IL-10 mRNA was upregulated throughout the treatment. IL-10 was functionally active because its neutralization improved IFN-γ and IL-13 mRNA expression in vitro. The IL-10/IFN-γ ratio was shown to be lower in patients who developed ADAs solely at the early infusions. IL-10 production consistently preceded or paralleled the IFN-γ onset in ADA- patients, while it was not produced or followed IFN-γ onset in ADA+ patients. In conclusion, this study provides evidence that the majority of exposed patients undergo a cellular response to IFX with the upregulation of IL-10. The development of ADA is associated with the early impairment of IL-10 and low levels of the IL-10/IFN-γ ratio.