Antibody Response to COVID-19 Booster Vaccination in Healthcare Workers.

Objective: To evaluate the mean increase of anti-S IgG antibody titer between the basal, pre-booster level to the titer assessed 14 days after the booster dose of BNT162b2. Patients and Methods: The RENAISSANCE study is an observational, longitudinal, prospective, population-based study, conducted on healthcare workers of Niguarda Hospital in Milan, Italy who received a BNT162b2 booster dose at least 180 days after their second dose or after positivity for SARS-CoV-2 and accepted to take part in the study. The RENAISSANCE study was conducted from January 1, 2021 through December 28, 2021. Findings: 1,738 subjects were enrolled among healthcare workers registered for the booster administration at our hospital. Overall, 0.4% of subjects were seronegative at the pre-booster evaluation, and 1 subject had a titer equal to 50 AU/ml: none of the evaluated subjects was seronegative after the booster dose. Thus, the efficacy of the booster in our population was universal. Mean increase of pre- to post-booster titer was more significant in subjects who never had SARS-CoV-2 (44 times CI 95% 42-46) compared to those who had it, before (33 times, CI 95% 13-70) or after the first vaccination cycle (12 times, CI 95% 11-14). Differently from sex, age and pre-booster titers affected the post-booster antibody response. Nevertheless, the post-booster titer was very similar in all subgroups, and independent of a prior exposure to SARS-CoV-2, pre-booster titer, sex or age. Conclusion: Our study shows a potent universal antibody response of the booster dose of BNT162b2, regardless of pre-booster vaccine seronegativity.

Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNe-short- And long-term Immune reSponSe evAluatioN in health Care workErs.

OBJECTIVE: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. METHODS: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription-polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. RESULTS: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. CONCLUSION: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.

Algorithm for Individual Prediction of COVID-19-Related Hospitalization Based on Symptoms: Development and Implementation Study.

BACKGROUND: The COVID-19 pandemic has placed a huge strain on the health care system globally. The metropolitan area of Milan, Italy, was one of the regions most impacted by the COVID-19 pandemic worldwide. Risk prediction models developed by combining administrative databases and basic clinical data are needed to stratify individual patient risk for public health purposes. OBJECTIVE: This study aims to develop a stratification tool aimed at improving COVID-19 patient management and health care organization. METHODS: A predictive algorithm was developed and applied to 36,834 patients with COVID-19 in Italy between March 8 and the October 9, 2020, in order to foresee their risk of hospitalization. Exposures considered were age, sex, comorbidities, and symptoms associated with COVID-19 (eg, vomiting, cough, fever, diarrhea, myalgia, asthenia, headache, anosmia, ageusia, and dyspnea). The outcome was hospitalizations and emergency department admissions for COVID-19. Discrimination and calibration of the model were also assessed. RESULTS: The predictive model showed a good fit for predicting COVID-19 hospitalization (C-index 0.79) and a good overall prediction accuracy (Brier score 0.14). The model was well calibrated (intercept -0.0028, slope 0.9970). Based on these results, 118,804 patients diagnosed with COVID-19 from October 25 to December 11, 2020, were stratified into low, medium, and high risk for COVID-19 severity. Among the overall study population, 67,030 (56.42%) were classified as low-risk patients; 43,886 (36.94%), as medium-risk patients; and 7888 (6.64%), as high-risk patients. In all, 89.37% (106,179/118,804) of the overall study population was being assisted at home, 9% (10,695/118,804) was hospitalized, and 1.62% (1930/118,804) died. Among those assisted at home, most people (63,983/106,179, 60.26%) were classified as low risk, whereas only 3.63% (3858/106,179) were classified at high risk. According to ordinal logistic regression, the odds ratio (OR) of being hospitalized or dead was 5.0 (95% CI 4.6-5.4) among high-risk patients and 2.7 (95% CI 2.6-2.9) among medium-risk patients, as compared to low-risk patients. CONCLUSIONS: A simple monitoring system, based on primary care data sets linked to COVID-19 testing results, hospital admissions data, and death records may assist in the proper planning and allocation of patients and resources during the ongoing COVID-19 pandemic.

Emergency attendance for acute hyper- and hypoglycaemia in the adult diabetic population of the metropolitan area of Milan: quantifying the phenomenon and studying its predictors.

BACKGROUND: We quantified, among diabetic adults, the frequency, costs, and factors associated with visits to the emergency department (EDs) and subsequent hospitalizations for acute hypoglycaemic and hyperglycaemic events. METHODS: We included adults with diabetes residing in the Milan Agency for Health Protection between 2015 and 2017. From healthcare databases, we identified demographic variables, comorbidities, type of treatment, insulin treatment duration, previous ED attendances for acute glycaemic events, and two indicators of glycaemic monitoring. Using a validated ICD-9-CM coding algorithm, we identified all ED attendances for acute glycaemic events from the ED database and calculated their incidence. We computed the direct costs from health databases and presented them as average annual mean costs for those having had at least an ED attendance. The analysis of the association between the number of ED attendances and potential determinants was performed using zero-inflated negative binomial regression models. These two-part models concomitantly estimate two sets of parameters: the odds-ratios (ORs) of having no attendances and the incidence rate ratios (IRRs) of attendance. RESULTS: The cohort included 168,285 subjects, 70% of subjects were older than 64 years, 56% were males, and 26% were treated with insulin. The incidence of acute glycaemic events for those attending the ED was 7.0 per 1000 patient-years, followed by hospitalization 26.0% of the time. The total annual direct cost for ED attendances due to acute glycaemic events was 174,000 €. Type of antidiabetic treatment had the strongest association with ED attendances for hypoglycaemia. Patients assuming insulin only had a lower probability of having no attendances (OR compared to those who assumed non-insulin antidiabetic drugs =0.01, 95% CI = 0.00-0.02). These patients also had the highest rate of hyperglycaemic episodes (IRR = 7.7, 95% CI = 5.1-11.7 for insulin only vs. non-insulin antidiabetic drugs). Subjects having had a previous episode of the same type leading to an ED visit had a higher rate of subsequent attendances (IRR for hypoglycaemia = 5.3, 95% CI = 3.9-7.3 and IRR for hyperglycaemia = 3.7, 95% CI = 1.3-10.2). CONCLUSION: Insulin treatment and having had a prior acute glycaemic event leading to an ED visit were major predictors of ED attendance for hyper and hypoglycaemia in a population of adults with diabetes.

Large community-acquired Legionnaires' disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018.

In July 2018, a large outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case-control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5-6 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case-control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic.

Do autistic patients change healthcare services utilisation through the transition age? An Italian longitudinal retrospective study.

OBJECTIVES: This paper aims to provide an estimate of the prevalence rate of autism spectrum disorder (ASD) in 8-year-olds in 2017 based on administrative databases and to investigate the change in healthcare service use during the healthcare transition age of 18. DESIGN: This research is based on a longitudinal retrospective cohort study. SETTING: The data is drawn from the Italian Administrative Healthcare Database (2010-2017). PARTICIPANTS: We identified 5607 ASD patients; 331 ASD patients from 2012 to 2015 in the calendar year of their 18th birthday were selected and their health service utilisation during a 5-year period-ranging from 2 years preceding and succeeding their 18th year-were investigated. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence, incidence and proportion of ASD patients receiving specific healthcare services were included in the outcome measures. RESULTS: Prevalence of ASD at age 8 was 5.4/1000. Global access to health and social services was lower both before and after age 18 (46.5% at 16; 68.0% at 18; 54.1% at 20). The percentage of patients receiving a neuropsychiatric consultation decreased after age 18 (30.8% at 18; 5.4% at 20). Community mental health services (CMHS) utilisation rate increased above 18 years of age. Regarding psychiatric visits, for both outpatient and CMHS, an increase was observed from 17.8% at age 18 to 25.4% at age 20. The utilisation of rehabilitation services decreased with age, dropping from 17.8% at age 16 to 1.8% at age 20. Psychiatric outpatient services remained stable across ages at about 14%. CONCLUSION: Our findings suggest that ASD patients changed clinical reference services with age from neuropsychiatric and rehabilitative services towards psychiatric and community-based services as they transitioned from paediatric to adult healthcare services.

[Mortality in the population surrounding an aluminum foundry in Eastern Piedmont, Italy, 1980-2017]. / Studio epidemiologico sub comunale nel Comune di Carisio (Piemonte, provincia di Vercelli ) sede di una fonderia di alluminio: analisi della mortalità dal 1980 al 2017.

An aluminum foundry has been present in the area of the district of Carisio (Piedmont region), Italy since 1975. Environmental analyses have shown that toxic emissions (in particular of dioxin) affect the district of Crocicchio and not the remaining municipality of Carisio. A study was therefore conducted to assess mortality in the population of Carisio and in the rest of the municipality, from 1980 to 2017, by using the Piedmont region as standard population. Excess mortality was found in the Crocicchio district for tumors (+ 88%), lung cancer in men (+ 320%) and total digestive tract tumors (+ 85%). Relative risks also show a higher risk of death caused by the above tumors, with two deaths per year being due to the existing environmental risk. An epidemiological and environmental monitoring plan should be implemented for the years to follow, and measures for the containment of polluting emissions from the site should be introduced immediately.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy.

PURPOSE:: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. METHODS:: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. RESULTS:: No significant differences in PSV, PI, or RI values were observed among the groups. CONCLUSION:: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy

Abstract Purpose: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. Methods: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. Results: No significant differences in PSV, PI, or RI values were observed among the groups. Conclusion: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

[Barriers and facilitators to the implementation of computerized decision support systems in Italian hospitals: a grounded theory study]. / Barriere e facilitatori all'implementazione dei sistemi di supporto decisionale computerizzati in ospedale: uno studio "grounded theory".

INTRODUCTION: Computerized Decision Support Systems (CDSSs) connect health care professionals with high-quality, evidence-based information at the point-of-care to guide clinical decision-making. Current research shows the potential of CDSSs to improve the efficiency and quality of patient care. The mere provision of the technology, however, does not guarantee its uptake. This qualitative study aims to explore the barriers and facilitators to the use of CDSSs as identified by health providers. METHODS: The study was performed in three Italian hospitals, each characterized by a different level of familiarity with the CDSS technology. We interviewed frontline physicians, nurses, information technology staff, and members of the hospital board of directors (n=24). A grounded theory approach informed our sampling criteria as well as the data collection and analysis. RESULTS: The adoption of CDSSs by health care professionals can be represented as a process that consists of six "positionings," each corresponding to an individual's use and perceived mastery of the technology. In conditions of low mastery, the CDSS is perceived as an object of threat, an unfamiliar tool that is difficult to control. On the other hand, individuals in conditions of high mastery view the CDSS as a helpful tool that can be locally adapted and integrated with clinicians' competences to fulfil their needs. In the first positionings, the uptake of CDSSs is hindered by representational obstacles. The last positionings, alternatively, featured technical obstacles to CDSS uptake. DISCUSSION: Our model of CDSS adoption can guide hospital administrators interested in the future integration of CDSSs to evaluate their organizational contexts, identify potential challenges to the implementation of the technology, and develop an effective strategy to address them. Our findings also allow reflections concerning the misalignment between most Italian hospitals and the current innovation trends toward the uptake of computerized decision support technologies.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. RESULTS: We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats

PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. RESULTS: We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats. .