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Supplementary Table from Plasma miR-151-3p as a Candidate Diagnostic Biomarker for Head and Neck Cancer: A Cross-sectional Study within the INHANCE Consortium

Background:Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium.Methods:A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test.Results:We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls.Conclusions:We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status.Impact:The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.

The aim of this study is to investigate the prognostic role of body mass index (BMI) and survival from head and neck cancer (HNC). We performed a pooled analysis of studies included in the International Head and Neck Cancer Epidemiology consortium in order to investigate the prognostic role of BMI and survival from HNC. We used Cox proportional hazards models to estimate the adjusted hazard ratios (HR) for overall survival and HNC-specific survival, by cancer site. The study included 10,177 patients from 10 studies worldwide. Underweight patients had lower overall survival (HR = 1.69, 95%CI: 1.31–2.19) respect to those having normal weight with consistent results across the HNC sites. Overweight and obese patients with oropharyngeal cancers had a favourable HNC-specific survival (HR = 0.50 (95%CI: 0.33–0.75) and HR = 0.51 (95%CI: 0.36–0.72), respectively). Among ever smokers overweight and obese patients showed a favourable HNC-specific survival (HR = 0.69 (95%CI: 0.56–0.86) and HR = 0.70 (95%CI: 0.61–0.80)). Our findings show that high BMI values at cancer diagnosis predict the survival rates in smoking patients with HNC. This association may be explained by residual confounding, reverse causation, and collider stratification bias, but may also suggest that a nutritional reserve may help patients survive HNC cancer.

PURPOSE: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. METHODS: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). RESULTS: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. CONCLUSION: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.

Purpose SARS-COV-2 pandemic led to antibiotic overprescription and unprecedented stress on healthcare systems worldwide. Knowing the comparative incident risk of bloodstream infection due to multidrug-resistant pathogens in COVID ordinary wards and intensive care-units may give insights into the impact of COVID-19 on antimicrobial resistance. Methods Single-center observational data extracted from a computerized dataset were used to identify all patients who underwent blood cultures from January 1, 2018 to May 15, 2021. Pathogen-specific incidence rates were compared according to the time of admission, patient’s COVID status and ward type. Results Among 14,884 patients for whom at least one blood culture was obtained, a total of 2534 were diagnosed with HA-BSI. Compared to both pre-pandemic and COVID-negative wards, HA-BSI due to S. aureus and Acinetobacter spp. (respectively 0.3 [95% CI 0.21–0.32] and 0.11 [0.08–0.16] new infections per 100 patient-days) showed significantly higher incidence rates, peaking in the COVID-ICU setting. Conversely, E. coli incident risk was 48% lower in COVID-positive vs COVID-negative settings (IRR 0.53 [0.34–0.77]). Among COVID + patients, 48% (n = 38/79) of S. aureus isolates were resistant to methicillin and 40% (n = 10/25) of K. pneumoniae isolates were resistant to carbapenems. Conclusions The data presented here indicate that the spectrum of pathogens causing BSI in ordinary wards and intensive care units varied during the pandemic, with the greatest shift experienced by COVID-ICUs. Antimicrobial resistance of selected high-priority bacteria was high in COVID positive settings.

Objective In this study, we evaluated the safety of early discharge (ED) of newborns born to coronavirus disease 2019 (COVID-19)-positive mothers. Study Design All ED newborns from the postpartum wards of the Fondazione Policlinico Gemelli between January 1, 2022, and February 28, 2022, were retrospectively analyzed. Newborns from mothers with COVID-19 and those from uninfected mothers were considered. The primary outcome was to evaluate whether the rate of the composite outcome, which was the percentage of rehospitalization/access in emergency room (RH/ER) within the first week from discharge, differed between neonates born to mother with COVID-19 (COVID-19 group) and those born to uninfected mothers (no COVID-19 group). The secondary outcomes were to assess the quality of feeding and number of outpatient visits in the follow-up clinic between the two cohorts of patients. Results One hundred and thirty-four newborns in the no COVID-19 group and 26 in the COVID-19 group were analyzed. The rate of RH/ER in the no COVID-19 group was of 6 over 134 newborns (0.045, 95% confidence image [CI]: 0.017–0.095), while in COVID-19 group, it was of 2 over 26 newborns (0.077), which does not differ from the expected rate (1.17 over 26 newborns, 0.045, 95% CI: 0.017–0.095). Conclusion ED for newborns from mothers with COVID-19 could be an actionable safe strategy. Key Points

Purpose During the early weeks of life optimization of nutrition in extremely preterm infants presents a critical opportunity to attenuate the adverse neurologic consequences of prematurity and potentially improve neurodevelopmental outcome. We hypothesized that the use of multicomponent lipid emulsion (MLE) in PN would be related to larger volume of the cerebellum on brain magnetic resonance at term of equivalent age (TEA) in extremely low birthweight (ELBW) infants. Methods We analyzed the brain Magnetic Resonance Imaging (MRI) at TEA of a cohort of preterm infants with gestational age (GA) ≤28 weeks and/or birthweight (BW) Results MRIs at TEA of 34 infants were then analyzed: 17 in the MLE group and17 in the SLE group. The postmenstrual age (PMA) at which MRIs were performed were comparable between the two study groups. The CeV, as well as the PMA-corrected CeV, were significantly higher in the MLE group than in the SLE group. No difference was found among the other brain volumes considered. Conclusion Our results suggest that the use of MLE in PN could promote CeV growth in ELBW infants, valued with MRI at TEA.

Introduction. Nitrous oxide (N2O) is widely used to induce sedation also outside of operating rooms; there is a chance of workplace exposures for the operators engaged in the outpatient use of nitrous oxide. The aim of this research is to assess nitrous oxide exposure in gastroenterology outpatient settings. Methods. We performed an observational study marked by N2O environmental testing in a gastroenterology outpatient care; environmental research was supported by biological monitoring with urinary N2O analysis in exposed operators. The research was conducted both without and using a collective security device (NIKI mask). Results. The study was rolled out in 10 sessions of day shift procedures, totaling 4105 samples. The average N2O concentration in the environment was 27.58 (SD 1.76) and 449.59 (SD 35.29), respectively with and without NIKI Mask; the distribution of gases in the environment under investigation was not homogeneous (Anovatest P=0.001). Biological testing revealed a substantial rise in urinary concentration of 8.97 (p=0.001) between the start and the end of the shift, and the use of the NIKI-mask was effective (p=.003). Discussion. The exposure levels reported exceed the limits of 50 ppm (Italy operating rooms threshold value) as well as the value of 25 ppm (NIOSH threshold-value), indicating a significant issue in the outpatient use of N2O. Technical measures are needed to contain the occupational risk from N2O exposure outside of operating rooms; for the exposure results detected in this research, it is also evident that workers exposed to N2O must be subject to adequate health surveillance accounting for this occupational risk.

The SARS-CoV-2 pandemic made the use of facemasks mandatory to prevent contact with the virus. Recent studies have revealed that intensive use of facemasks significantly exacerbated pre-existing headaches and triggered de novo headaches. In our experience, some subjects also complain of symptoms of neuropathic pain in the head/facial regions. Until now, the relationship between neuropathic pain and facemasks has not been documented. The aim of the study is to investigate the occurrence of neuropathic pain related to facemask use. It is a cross-sectional survey using a questionnaire, developed following a commonly accepted outcome research methodology. Participants, both health care and non-health care workers, responded to items included in the questionnaire about the type of facemasks, time and manner of wearing them, side effects such as skin lesions, symptoms of neuropathic pain, etc.

In order to reduce the burden on healthcare systems and to support differential diagnosis with COVID-19, influenza and pneumococcal vaccinations were strongly recommended during the COVID-19 pandemic, especially in vulnerable groups. However, no univocal and conclusive evidence on the relationship between influenza and pneumococcal vaccinations and COVID‐19 outcomes exists. We evaluated the association between such vaccinations, COVID-19 hospitalization, intensive care unit admissions and deaths in a cohort (N = 741) of COVID-19 patients who had access to the emergency room of a large Italian University hospital between March 1, 2020 and June 1, 2020. Results show that influenza and pneumococcal vaccinations did not affect hospitalization, intensive care unit admission and deaths in COVID-19 patients in the overall sample and in those ≥ 65 years. The same pattern of results was confirmed considering timing of influenza vaccine administration, vaccination type, and number of uptakes in the last five vaccination campaigns. In conclusion, our study does not support an impact of influenza and pneumococcal vaccinations on COVID-19 outcomes.

BackgroundProgressive advances in technologies for DNA sequencing and decreasing costs are allowing an easier diffusion of genetic and genomic tests. Physicians’ knowledge and confidence on the topic is often low and not suitable for manage this challenge. Tailored educational programs are required to reach a more and more appropriate use of genetic technologies.MethodsA distance learning course has been created by experts from different Italian medical associations with the support of the Italian Ministry of Health. The course was directed to professional figures involved in prescription and interpretation of genetic tests. A pretest-post-test study design was used to assess knowledge improvement. We analyzed the proportion of correct answers for each question pre and post-test, as well as the mean score difference stratified by gender, age, professional status and medical specialty.ResultsWe reported an improvement in the proportion of correct answers for 12 over 15 questions of the test. The overall mean score to the questions significantly increased in the post-test, from 9.44 to 12.49 (p-value < 0.0001). In the stratified analysis we reported an improvement in the knowledge of all the groups except for geneticists; the pre-course mean score of this group was already very high and did not improve significantly.ConclusionDistance learning is effective in improving the level of genetic knowledge. In the future, it will be useful to analyze which specialists have more advantage from genetic education, in order to plan more tailored education for medical professionals.

The association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC.Data from three studies of the StoP Project with available information on metformin intake were analyzed. Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model. The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials.The OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants' characteristics or when restricting the analyses to those with a history of diabetes. The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake.The results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.

Objective The extent of vertical transmission (VT) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mothers their fetuses or neonates is still uncertain. We aimed to determine the incidence of VT. Study Design In this prospective cohort study. All mother diagnosed with SARS-CoV-2 infection at the time of delivery or up to 1 week prior and their neonates, managed in a tertiary referral hospital for pregnancy complicated by coronavirus disease 2019 (COVID-19) in Rome, from April 2 to December 22, 2020, were included. Maternal infection was defined as nasopharyngeal swab test results positive for SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR). Biological samples were collected before, at, and after delivery to test positivity for SARS-CoV-2 RT-PCR and anti-SARS-CoV-2-specific antibodies. Results The cohort included 95 women and 96 neonates with documented SARS-CoV-2 test results. Four neonates (4.2%) tested positive. The incidence of VT, according to the guidance criteria for diagnosing perinatal SARS-CoV-2 infection, was 5.2%. Neonatal symptoms were due to prematurity or fetal distress: symptomatic infants had lower median (min–max) gestational age, 38.1 (29.3–40.6) versus 39.3 (33.9–41.9) weeks (p = 0.036), and 1-minute and 5-minute Apgar scores, 9 (3–9) versus 9 (7–10) (p = 0.036) and 10 (6–10) versus 10 (8–10) (p = 0.012), respectively, than asymptomatic infants and needed more frequent assistance in the delivery room (22.2 vs 2.5%; p = 0.008). Only six (7.1%) neonates had anti-SARS-CoV-2-specific antibodies, despite the ongoing maternal infection. Conclusion The incidence of VT is low as is the detection of specific anti-SARS-CoV-2 antibodies in cord blood when infection is contracted late in pregnancy. This would suggest poor protection of infants against horizontal transmission of the virus. Key Points

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Background Mechanical ventilation is still needed in most preterm newborns, even in the non-invasive ventilation era. Ventilator-induced lung injury is one of the known pathogenetic factors of bronchopulmonary dysplasia (BPD) in preterm newborns. Lung injury has several patterns including surfactant dysfunction. Some recent trials have showed that a late surfactant administration can improve respiratory outcome in preterm babies still on invasive ventilation after the first week of life. Unfortunately, these results are still not conclusive. Moreover, giving surfactant after a recruitment manoeuvre in High Frequency Oscillatory Ventilation (HFOV) was shown to be safe and to reduce mortality in extremely preterm infants in a recent RCT. Our aim is to test the hypothesis that endotracheal administration of poractant-alfa preceded by a recruitment manoeuvre in HFOV in preterm infants still requiring mechanical ventilation at 7-10 days of life could facilitate extubation. Methods/Design: This will be an unblinded monocentric pilot trial that will be conducted in a III level Neonatal Intensive Care Unit at Fondazione Policlinico Agostino Gemelli IRCCS in Rome - Italy. Preterm newborns with a gestational age < 28 weeks still requiring invasive mechanical ventilation at 7-10 days of life with a fraction of inspired oxygen (FiO2) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours will be eligible for the study. Patients will be randomly assigned to intervention or to standard care. Intervention group infants will receive up to 4 doses of Poractant-alfa every 12 hours, each dose preceded by a recruitment manoeuvre in HFOV, until extubation. Primary endpoint will be the first successful extubation. Discussion Surfactant therapy is nowadays recommended in case of RDS in the first days of life but little is known about its effects in ventilator-dependant preterm newborns. Late administration of surfactant could help healing the lung of preterm babies in which RDS is evolving in a chronic pulmonary insufficiency of prematurity. The findings of this pilot trial will permit evaluation of the study design for a full-scale RCT. Trial registration: Clinicaltrials.gov – ID NCT04825197. Registered 12 April 2021, https://clinicaltrials.gov/ct2/home

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. Methods: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman–Tukey double arcsine transformation, and 95% CIs were calculated using Clopper–Pearson exact CIs in all instances. Results: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3–4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61–0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. Conclusions: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.

ObjectiveTo evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS).DesignObservational study.SettingTertiary neonatal intensive care unit.PatientsTwenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life.InterventionsAll infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany).Main Outcome MeasuresVariations and fluctuations of delivered high-frequency tidal volume (VThf), fluctuation of pressure amplitude (ΔP) and partial pressure of CO2 (pCO2) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants.ResultsThere were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VThf per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VThf/Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg, p < 0.0001) with significantly lower pCO2 levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg, p = 0.01), 54.4% of patients having pCO2 below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH2O) than in HFOV + VG group (13 ± 3 cmH2O, p = 0.01).ConclusionHFOV + VG maintains pCO2 levels within target range and reduces VThf delivered variations more consistently than HFOV alone after surfactant administration.

Costello syndrome (CS) is a rare disorder caused by activating dominantly acting germline variants in the HRAS gene. CS is defined by a clinical phenotype characterized by a distinctive gestalt, multiple congenital anomalies, and increased risk to develop tumors. Hypoglycemia and hypercholesterolemia have been reported to occur in affected individuals, but the underlying molecular events remain to be characterized. Here, we provided data on glucose/lipid metabolism and amino acid profile of a large single-center cohort of individuals affected by CS to systematically assess the extent of metabolic dysregulation characterizing this disorder and optimize patient management.

Background. Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. Methods. History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth’s penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. Results. History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07–4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77–1.39). Conclusions. In the pooled analysis of 11 case–control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.

BackgroundMost countries initially deployed COVID-19 vaccines preferentially in elderly populations. Population-level vaccine effectiveness may be heralded by an increase in the proportion of deaths among non-elderly populations that were less covered by vaccination programs.MethodsWe collected data from 40 countries on age-stratified COVID-19 deaths during the vaccination period (1/14/2021-5/31/2021) and two control periods (entire pre-vaccination period and excluding the first wave). We meta-analyzed the proportion of deaths in different age groups in vaccination versus control periods in countries with low vaccination rates; (2) countries with age-independent vaccination policies; and (3) countries with standard age-dependent vaccination policies.FindingsCountries that prioritized vaccination among older people saw an increasing share of deaths among 0-69 year old people in the vaccination versus the two control periods (summary prevalence ratio 1·32 [95 CI% 1·24-1·41] and 1·35 [95 CI% 1·26-1·44)]. No such change was seen on average in countries with age-independent vaccination policies (1·05 [95 CI% 0·78-1·41 and 0·97 [95 CI% 0·95-1·00], respectively) and limited vaccination (0·93 [95 CI% 0·85-1·01] and 0·95 [95 CI% 0·87-1·03], respectively). Prevalence ratios were associated with the difference of vaccination rates in elderly versus non-elderly people. No significant changes occurred in the share of deaths in age 0-49 among all 0-69 deaths in the vaccination versus pre-vaccination periods.InterpretationThe substantial shift in the age distribution of COVID-19 deaths in countries that rapidly implemented vaccination predominantly among elderly may herald the population level-effectiveness of COVID-19 vaccination and a favorable evolution of the pandemic towards endemicity with fewer elderly deaths.FundingThis study received no specific funding.

Background: Due to its high incidence, evaluating performance of care delivered to breast cancer patients is a crucial issue. The multidisciplinary panel E.Pic.A. (Economic Appropriateness of an Integrated Care Pathway) defined a set of key performance indicators (KPIs) to evaluate economic waste in breast cancer healthcare interventions. Methods: The E.Pic.A. panel identified the principal KPIs that are crucial within the breast cancer care pathway to evaluate the performance of care. KPIs were defined taking into account their reliability, validity, usability and feasibility of measurement through the linkage between multiple routine healthcare data sources. Results: Seven KPIs were identified: three on instrumental diagnostics, two on surgery and two on treatment. The three KPIs regarding instrumental diagnostics are aimed at assessing the inappropriateness of diagnostic tests performed before and after the index surgery. The two KPIs regarding surgery measure the inappropriateness of possible repeated interventions considering the time elapsed from the index surgery. The two KPIs regarding oncologic therapy measure the inappropriateness about the administration time of adjuvant therapy and radiotherapy considering the time elapsed from the index surgery. Conclusion: E.Pic.A methodology could help to evaluate economic waste in healthcare interventions with the objective of redirecting resources to interventions with greater value. (HTA & Market Access)

Severe Acquired Brain Injury (sABI) is a leading cause of disability and requires intensive rehabilitation treatment. Discharge from the rehabilitation ward is a key moment in patient management. Delays in patient discharge can adversely affect hospital productivity and increase healthcare costs. The discharge should be structured from the hospital admission toward the most appropriate environment. The purpose of our study is to investigate early predictors of outcome for discharge in older adults with sABI. A retrospective study was performed on 22 patients who were admitted to an intensive neurorehabilitation unit between June 2019 and December 2021. Patients were divided into two outcome categories, good outcome (GO) or poor outcome (PO), based on discharge destination, and the possible prognostic factors were analyzed at one and two months after admission. Among the factors analyzed, changes in the Disability Rating Scale (DRS) and Level of Cognitive Functioning (LCF) at the first and second month of hospitalization were predictive of GO at discharge (DRS, p = 0.025; LCF, p = 0.011). The presence of percutaneous endoscopic gastrostomy at two months after admission was also significantly associated with PO (p = 0.038). High Body Mass Index (BMI) and the presence of sepsis at one month after admission were possible predictors of PO (BMI p = 0.048; sepsis p = 0.014). An analysis of dynamic predictors could be useful to guarantee an early evaluation of hospital discharge in frail patients with sABI.

Background: Nitrous oxide is widely used to induce sedation; however, its use outside of operating rooms – such as in ambulatory rooms – is not properly controlled by norms. In the lack of supervision, there is a chance of workplace exposures for the operators engaged in the outpatient use of nitrous oxide. The aim of this research is to assess nitrous oxide exposure in gastroenterology outpatient settings. Methods: We performed an observational study with a first step marked by nitrous oxide environmental testing in a gastroenterology outpatient care where colonoscopies were practiced; environmental research was supported by biological monitoring with urinary N2O analysis in exposed operators. The research was conducted in the absence and then in the presence of a collective security device (Niki mask). Results: The study was rolled out in 10 sessions of day shift procedures, totaling 4105 samples. The average nitrous oxide concentration in the environment was 27.58 (SD 1.76) and 449.59 (SD 35.29), respectively with and without Niki Mask; the distribution of gases in the environment under investigation was not homogeneous (Anova test p.001). Biological testing revealed a substantial rise in urinary concentration of 8.97 (p.001) between the start and the end of the shift, and the use of the Niki mask was effective (p=.003). Conclusions: The exposure levels reported in environmental sampling exceed the limits of 50 ppm (the value set for operating rooms in Italy) as well as the value of 25 ppm (NIOSH threshold value), indicating a significant issue in the outpatient use of nitrous oxide. It is evident that technical measures are needed to contain the occupational risk from Nitrous oxide exposure outside of operating rooms, and that even the basic use of Niki masks would not be sufficient to minimize professional exposure and protect workers; for the exposure results detected in this research, it is also plain that exposures must be subject to health surveillance.

In several hospitals worldwide, healthcare workers are currently at the forefront against coronavirus disease 2019 (COVID-19). Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS has been enlisted as a COVID hospital, healthcare workers deployed to COVID wards were separated from those with limited or no exposure, whereas administrative staff was destined to work-from-home. Between June 4 and July 3 2020, an investigation was carried out to evaluate seroprevalence of SARS-CoV-2 IgG antibodies among employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity and predictive values were determined with reverse-transcription polymerase chain reaction (RT-PCR) on nasal/oropharyngeal swabs as gold standard.Four thousand, seven hundred seventy-seven participants were enrolled. Seroprevalence was 3.66% using the POC test and 1.19% using venous blood test, with a significant difference between the two (p < 0.05).POC sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among low-risk population, point-of-care’s predictive values were 58.33% (positive) and 98.23% (negative) whereas venous blood test’s were 92.86% (positive) and 98.53% (negative). In conclusion, point-of-care tests have low diagnostic accuracy, while venous blood tests seem to show an overall poor reliability.

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04, I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82, 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38, 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92, 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62, 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.

The effectiveness of virtual reality (VR) in the motor and cognitive rehabilitation of patients with severe acquired brain injury (sABI) is unclear. This randomized, controlled, crossover, single-blinded, pilot study investigates the cognitive and motor effects of lower limb robotic therapy with and without VR visual feedback in a group of patients with ABI. A total of 23 patients with ABI were randomized into two groups: one group (VR-NVR) underwent a 2-week rehabilitation for the lower limbs training with a robotic device (Omego®) with VR feedback, followed by 2 weeks without VR; the other group (NVR-VR) performed the protocol in the opposite order. Patients were evaluated at baseline, after two and four weeks of treatment using the Level of Cognitive Functioning scale (LCF), Disability Rating Scale (DRS), and Motricity Index for Lower Limb (MI-LL) in the most affected limb. At the end of the intervention, both groups significantly improved in all the outcomes. A significant difference was found between VR treatment versus non-VR treatment for LCF (p = 0.024) and for DRS (p = 0.043) after the second week, while no significant differences were found in the group NVR-VR at T1. Our study indicates how the combination of robotic treatment with VR is effective in enhancing the recovery of cognitive function in patients with ABI, also improving disability and muscular function. Further, VR seems to enhance the early recovery process of motor and cognitive functions.

The last fifteen years have seen the emergence of Public Health Genomics (PHG), a multidisciplinary field related to the effective and responsible translation of genome-based knowledge and technologies to improve population health. While at the beginning the main concern of PHG was that genetic/genomic applications should be evaluated rigorously before entering into clinical and public health (PH) practice, now the main matter is around the fact that there are some genetic/genomic applications with proved efficacy and cost-effectiveness that should be implemented and become citizens’ rights. In any case, there is a critical need for a robust evaluation process, that takes into account also context-related dimensions (delivery models, economic evaluation and organizational aspects) to facilitate the implementation of these technologies. Systematic reviews of full economic evaluations of genetic/genomic applications are of paramount importance to identify all feasible health programs involving a defined use of a particular genetic/genomic application and to recognize which health programs can maximize the value of that genetic/genomic application. Cost-effectiveness analyses may be useful also in the early stages of the evaluation process to assess which characteristics of a genetic/genomic application need to be improved. Finally, the implementation of genetic/genomics applications requires specific training efforts for public health professional to increase their current level of competence. All these issues are addressed in this chapter, using the population health perspective and the point of view of PH.

Background Italy was the first European country to implement a national lockdown because of the COVID-19 pandemic. Worldwide, this pandemic had a huge impact on the mental health of people in many countries causing similar reaction in terms of emotions and concerns at the population level. Our study investigated the impact of the COVID-19 pandemic on psychological well-being in a cohort of Italian university students. Methods We conducted a cross-sectional survey in the period immediately after the first lockdown through the administration of a questionnaire on the personal websites of students attending their undergraduate courses at the Università Cattolica del Sacro Cuore. We used the Patient-Health-Engagement-Scale, Self-Rating-Anxiety-Scale, and Self-Rating-Depression-Scale to assess engagement, anxiety symptoms, and depression symptoms of our sample. Results The sample size was 501 subjects, of which 35.33% were classified as anxious and 72.93% as depressed. Over 90% of respondents had good understanding of the preventive measures despite over 70% suffered from the impossibility of physically seeing friends and partners. Around 55% of students would have been willing to contribute much more to face the pandemic. An increase in the occurrences of anxiety was associated with being female, being student of the Rome campus, suffering from the impossibility of attending university, being distant from colleagues, and being unable of physically seeing one's partner. Performing physical activity reduced this likelihood. Conclusions University students are at risk of psychological distress in the case of traumatic events. The evolution of the pandemic is uncertain and may have long-term effects on mental health. Therefore, it is crucial to study the most effective interventions to identify vulnerable subgroups and to plan for acute and long-term psychological services to control and reduce the burden of psychological problems.

Head and neck cancer (HNC) represents the sixth most common cancer and the seventh cause of cancer-related deaths worldwide. Because of HNC high mortality and morbidity a support from the development of new biomarkers and personalized care for patients is needed. The role of micro-RNAs (miRs), as new epigenetic biomarkers, aimed at improving early diagnosis, predicting prognosis and establishing effective cancer therapies, has recently received considerable attention. The aim of this study was to conduct an umbrella review that synthetizes all the findings of systematic reviews already available in literature that investigate the prognostic role of miRs as potential biomarkers in the field of tertiary prevention of HNC. We selected systematic reviews, published in English until December 2019, related to human HNC with meta-analysis of observational studies that reported quantitative prognostic measures, Hazard Ratios (HRs), of Overall Survival (OS) or Disease-Free Survival (DFS). The methodological quality of the included reviews was assessed using the Assessment of Multiple Systematic Reviews AMSTAR 2 tool. Six systematic reviews were included in the umbrella review. The most reported miRNAs were: miR21; the Let7 family (c,d,g), miR17, 18 family, 20a, 29 family, 125b, 375. A total of 4 reviews assessed miR-21 expression in HNC patients, all showing its upregulation. The most frequently studied miR was miR21 which was reported either in the OS and DFS statistical analyses. The OS analysis showed a significant lower prognosis when miR21 was upregulated. It is involved in oncogenic and oncosuppressive cell signals pathways: the overexpression of miR21 was shown to be associated with cell proliferation, migration, invasion and survival. Recently the cumulative effects of sets of miRs has been increasingly studied and they might be stronger predictor of survival than single. The role of miRNAs as a prognostic biomarker specifically in HNC still need to be investigated. Key messages Some miRs were demonstrated to have as tumor-suppressing and oncogenic roles according to their level of regulation (up/down-regulation) in Head and Neck cancer patients. The role of miRs as prognostic biomarkers in HNC patients still need to be addressed by performing large scale to verify and enhance the power of evidence and clinical utility of these.

Introduction Various single nucleotide polymorphisms (SNPs) have been associated with Head and Neck Cancer (HNC) susceptibility and prognosis. The pathogenesis of HNC is related to alterations in metabolite concentrations. Dietary intake may also influence the metabolic profile. We aimed to evaluate the association between serologic metabolites on the one hand and on the other hand HNC related SNPs and dietary intake. Methods This study included participants from the Erasmus Rucphen Family Study (ERF). We identified the SNPs associated with HNC from the GWAS Catalog, reaching genome-wide significance at P Results The study included 2758 participants, in whom 820 metabolites were analyzed. Four SNPs showed a significant association with circulating metabolites: rs174549 with phosphatidylcholine diacyl (β = 0.45; p-value= 7.17 × 10− 40), rs310518 with lipoprotein IDL sub-fraction, rs1229984 with triglycerides and rs1494961 with propionylcarnitine. The minor variant allele of the 4 SNPs showed increased level of the metabolites in blood. As to the association diet and metabolite concentration, significant associations were found for dairy products with sphingomyelin, fish intake with phosphatidylcholines, cholesterol esters with vegetables and myoinositol with fruits intake. When the results of both analyses were merged, 5 metabolites were found to be associated with dietary variables and rs174549. In the minor allele carriers, phosphatidylcholines increased with consumption of fish and phosphatidylethanolamine increased with consumption of diary products. Conclusions The genetic variants rs174549, which is a determinant of genetic HNC susceptibility, is associated with phosphatidylcholines and phosphatidylethanolamine in the circulation. Key messages In the minor allele carriers of rs174549, phosphatidylcholine diacyl level in circulation increased with consumption of fish. In the minor allele carriers of rs174549, phosphatidylethanolamine level in circulation increased with consumption of diary products.

Background Previous findings suggest there might be an inverse association between body mass index (BMI) and overall (OS) and Head and Neck-specific survival. The aim of this study was to investigate the prognostic role of BMI in the largest available cohort of HNC patients. Methods We performed a pooled analysis of studies participating at the INHANCE consortium. Cases were adults with HNCs of the oral cavity, oropharynx, hypopharynx and larynx. We used cox's proportional hazards models to estimate the relationship between BMI and overall and HNC-specific mortality. Sensitivity analysis were performed according to tumour location, smoking status and length of follow-up. Results The study included 9484 patients from 10 centres worldwide for a median follow-up of 48 months (IQR: 18-69). Overall 3623 patients (38.2%) died from all-causes and 1493 (15.7%) from HNC. Compared to patients with a normal weight, overweight or obese was associated with a longer HNC-specific survival (HR = 0.58, 95% CI: 0.35-0.95, HR = 0.37, 95% CI: 0.17-0.78, respectively), while underweight was associated to a shorter survival (HR = 1.73, 95% CI: 1.36-2.21). Results were heterogeneous according to tumour site, with the strongest effect among oropharynx and oral cavity cancer sites. When we restricted the analysis among patients with a follow-up longer than 5 years, underweight (HR = 5.17, 95% CI: 3.02-8.86) was associated with shorter HNC-specific survival. Conclusions Our findings suggest low BMI values are at diagnosis increase mortality in HNC patients. The protective effect of high BMI might be partially explained by residual confounding and reverse causality, so that further research is needed to clarify the potential role in tertiary prevention of BMI. Key messages BMI at diagnosis is a prognostic factor of HNC. Low BMI values predict unfavourable outcomes.

Objective Head and neck cancer (HNC) is the sixth leading cancer worldwide with approximately 600,000 new cases per year. Several studies suggest that HNC survivors may have an increased risk of developing second primary cancers (SPCs). A systematic review and meta-analysis was performed aiming to quantify the overall and site-specific risk of metachronous SPCs in HNC survivors. Methods PubMed, Web of Science and Scopus were searched to identify studies published until October 2019. Studies investigating the standardised incidence ratio (SIR) of metachronous SPC were included. A random-effects meta-analysis was performed to calculate the overall and site-specific SIRs. Newcastle-Ottawa Scale was used to assess the study's quality. Heterogeneity was quantified using the I2 statistics and explored using meta-regression. Results Twenty-six studies were included in the systematic review. Studies differed by the definition of metachronous SPC used. For the meta-analyses, the studies were grouped according to these definitions. In the three groups, the overall risk of metachronous SPC was increased. The highest SPC risk was for oropharynx, oesophagus and lung. Conclusions Head and neck cancer survivors are at increased overall risk of metachronous SPCs. The canonical upper aerodigestive sites, HNLE (head and neck, oesophagus and lung), were the SPC sites with the highest risk. Implication for cancer survivors Our results emphasise the importance of targeted surveillance strategies aimed at early detection and tertiary preventive interventions.

Background Physical activity (PA) has been recognized as a protective factor against several types of cancer, though robust evidence related to Gastric Cancer (GC) are lacking. This study aimed to establish whether leisure-time PA can prevent GC using data from a large pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project.Methods Five case-control studies from StoP project collected data on PA, for a total of 2,415 cases and 9,722 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Afterwards, we used a random-effect models for estimating pooled effect estimates. Heterogeneity across studies was assessed using Q and I 2 statistics. We performed stratified analyses according to demographic, lifestyle and clinical covariates.Results The pooled ORs for GC risk were 0.90 (95% CI: 0.72, 1.13) for intermediate, and 0.72 (95% CI: 0.57, 0.91) for high levels of leisure-time PA. There was no evidence of significant heterogeneity in outcome estimates ( I 2 = 49.7%; p=0.094 for intermediate; I 2 = 42.9%, p=0.135 for high levels of exposure). GC risk estimates did not differ across strata of selected covariates.Conclusions Our study is the largest pooled analysis that provides insights about protective effects of high levels of recreational PA on GC risk. Although our results should be confirmed from large cohort studies, the implications have relevant public health significance.

BackgroundAn individual’s lifetime risk of Coronary Artery Disease (CAD) is determined by a combination of genetic and lifestyle factors. Whilst adherence to a healthy lifestyle can help individuals with high genetic risk reduce their lifetime risk of CAD, the extent to which blood lipid levels affect CAD risk in individuals with varying genetic risk remains unknown. To explore how genetics, blood lipids and CAD risk interact, we derived a novel genome-wide polygenic risk score (PRS) for CAD. We then applied the PRS to individuals from the UK Biobank and divided them into Low PRS (bottom 10 percentiles of PRS distribution), Intermediate PRS (PRS in the 10th-90th percentiles), and High PRS (top 10 percentiles), and further stratified individuals by blood lipid levels.ResultsWe found that the elevated CAD risk conferred by high low-density lipoprotein cholesterol (LDL-C) was modified by the interaction with PRS (P-value interaction: 190 mg/dL; HR 2.77; 95% CI, 2.33-3.28). Furthermore, individuals with High PRS but whose lipid levels were below the following thresholds did not have a significantly increased risk for incident CAD: LDL-C 190 mg/dl) did not have increased CAD risk, which was comparable to individuals with Intermediate PRS and Optimal LDL-C (ConclusionsOur results have important implications for the primary prevention of coronary artery disease. Currently, healthy individuals with Borderline LDL-C (130-159 mg/dL) are not considered to be at high risk of CAD. Here we demonstrate that the combination of Borderline LDL-C and High PRS results in CAD relative risk which is greater than individuals without high polygenic risk, but whose LDL-C levels are high enough for statins to be recommended (>190 mg/dL). This analysis therefore demonstrates that PRS can identify a proportion of the population who are at high-risk of CAD but who are invisible to current approaches for assessing CAD risk. Moreover, of perhaps greater significance is the evidence that individuals who have a combination of High PRS and Optimal blood lipid levels do not have greater risk of CAD than individuals without high polygenic risk and the same Optimal blood lipid levels. Our results suggest that high polygenic risk for CAD could be overcome by controlling blood lipid levels. We propose that incorporating PRS into CAD risk assessment early in life could allow individuals at high polygenic risk to benefit from tailored blood lipid guidelines and avoid lifetime exposure to potentially damaging PRS-dependent LDL-C levels.

Italy was the first European country to implement a national quarantine, with 71 days of total lockdown as a result of the COVID-19 outbreak. This study investigated the effects of the COVID-19 pandemic on the mental health and psychological well-being of a sample of Italian university students. A cross-sectional survey was conducted in the period immediately following the end of lockdown through the administration of a questionnaire on the personal websites of students attending their undergraduate courses at Universita Cattolica del Sacro Cuore.The Patient Health Engagement Scale, the Self-Rating Anxiety Scale, and the Self-Rating Depression Scale were used to assess engagement, anxiety symptoms, and depression symptoms, respectively.The sample size was 501, of whom 35.33% were classified as anxious and 72.93% as depressed, although with a prevalence of mild symptoms. Over 90% of respondents reported understanding the preventive measures of the lockdown despite over 70% suffering from the impossibility of seeing their friends and partners. Over 55% of students would have been willing to contribute much more to facing the pandemic. An increase in the occurrences of anxiety was associated with being female, being students of the Rome campus (Central Italy), suffering from the impossibility of attending university, distance from colleagues, and the impossibility of seeing one’s partner. Performing physical activity reduced such a probability. Borderline risk factors for the occurrence of depression were being a student at the Rome campus and suffering from the distance to one’s fellow students. Funding Statement: No funding was received for this study. Declaration of Interests: All authors confirm that they have no conflicts of interest or competing interests. Ethics Approval Statement: The protocol of the study was approved by the Ethics Committee of the Policlinico Universitario A. Gemelli IRCCS and by the Internal Board of the University.

The early identification of gastric cancer (GC) represents a major clinical challenge. We conducted a systematic review of studies evaluating the miRNA expression profiling as a diagnostic tool in GC.We performed a search of PubMed, ISI Web of Science and SCOPUS databases for studies on diagnostic miRNAs and GC, published in English up to October 2017. Eligibility criteria included case-control studies evaluating blood or tissue-based miRNA expression profiles, and incorporating at least two detection phases (screening and validation).We included 27 eligible studies, that reported on 97 deregulated miRNAs either in blood or tissue, out of which 30 were reported in at least two studies. Among 22 studies on tissue-diagnostic miRNAs, 13 consistently upregulated miRNAs (miR-214, miR-21, miR-103, miR-107, miR-196a, miR-196b, miR-7, miR-135b, miR-222, miR-23b, miR-25, miR-92 and miR-93), and six consistently downregulated miRNAs (miR-148a, miR-375, miR-133b, miR-30a, miR-193a and miR-204) were reported. Ten miRNAs with inconsistent direction of expression in tissues were identified. Among the five studies performed on blood samples, only one miRNA was consistently upregulated (miR-20a).This review shows that some tissue or blood miRNAs may be considered as potential biomarkers for GC diagnosis, that urgently needs to be confirmed from large prospective studies.

Objective To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). Working hypothesis nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. Study design Multicenter non-blinded prospective randomized crossover study. Patient selection Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. Methodology Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. Results Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). Conclusions nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .

The objectives of the study were to calculate the standardised mortality rates (SMRs) for COVID-19 in European Union/European Economic Area countries plus the UK and Switzerland and to evaluate the correlation between SMRs and selected indicators in the first versus the subsequent waves until 23 June 2021. We used indirect standardisation (using Italy as the reference) to compute SMRs and considered 16 indicators of health and social well-being, health system capacity and COVID-19 response. The highest SMRs were in Belgium, the UK and Spain in the first wave (1.20–1.84) and in Hungary, Czechia and Slovakia in the subsequent waves (2.50–2.69). Human Development Index (HDI), life expectancy, urbanisation and healthcare expenditure had positive correlations with SMR in the first wave (rho=0.30–0.46), but negative correlations (rho=−0.67 to −0.47) in the subsequent waves. Retail/recreation mobility and transit mobility were negatively correlated with SMR in the first wave, while transit mobility was inversely correlated with SMR in the subsequent waves. The first wave hit most hard countries with high HDI, high life expectancy, high urbanisation, high health expenditures and high tourism. This pattern may reflect higher early community seeding and circulation of the virus. Conversely, in the subsequent waves, this pattern was completely inversed: countries with more resources and better health status did better than eastern European countries. While major SMR differences existed across countries in the first wave, these differences largely dissipated by 23 June 2021, with few exceptions.

IntroductionPrecision health requires citizens that are empowered to orient health decisions towards their personal values, aware of the benefits and risks, and committed to sharing their personal data to trustful institutions. Effective citizen engagement initiatives are fundamental for the success of a precision health approach.ObjectiveTo provide an overview of citizen engagement initiatives in precision health in European Union (EU) member states.DesignScoping review.MethodsThe electronic databases PubMed, Web of Science, CINAHL and Embase were searched to include articles published in English. Furthermore, desk research was conducted in English, Dutch, French, Italian and Spanish. Articles or reports regarding ongoing initiatives of citizen engagement in precision health conducted in EU member states and published from January 2015 to July 2020 were considered eligible. A quality assessment of the retrieved entries using Critical Appraisal Skills Programme tool was conducted.ResultsWe identified nine documents, which reported eight ongoing citizen engagement initiatives, with substantial variability. Government agencies, non-governmental organisations and scientific societies were the main organisers and funders. Most of the initiatives were conducted in the UK. Genomics was the most emphasised aspect of precision health in these initiatives. Among the identified initiatives, both in-person and digital means were reported.ConclusionOur work provides an overview of current citizen engagement initiatives in the EU that can be useful for stakeholders interested in designing and developing precision health projects enriched by meaningful citizen participation.PROSPERO registration numberCRD42020193866.