Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection.

The immune response after SARS-CoV-2 vaccine administration appears to be characterized by high inter-individual variation, even in SARS-CoV-2 positive subjects, who could have experienced different post-infection, unresolved conditions. We monitored anti-SARS-CoV-2 IgG levels and kinetics along with circulating biomarkers in a cohort of 175 healthcare workers during early immunization with COVID-19 mRNA-LNP BNT162b2 vaccine, to identify the associated factors. Subjects with a previous SARS-CoV-2 infection were characterized by higher BMI and CRP levels and lower neutrophil count with respect to naïve subjects. Baseline IgG levels resulted associated with CRP independently on BMI and inflammatory diseases. Among 137 subjects undergoing vaccination and monitored after the first and the second dose, three kinetic patterns were identified. The pattern showing a rapid growth was characterized by higher IgG levels at baseline and higher CRP and MCHC levels than negative subjects. Subjects previously exposed to SARS-CoV-2 showed higher levels of CRP, suggesting persistence of unresolved inflammation. These levels are the main determinant of IgG levels at baseline and characterized subjects belonging to the best performing, post-vaccine antibody kinetic pattern.

Prevalence of abdominal aortic aneurysms and its relation with cardiovascular risk stratification: protocol of the Risk of Cardiovascular diseases and abdominal aortic Aneurysm in Varese (RoCAV) population based study.

BACKGROUND: Recent meta-analyses suggested that screening program for abdominal aortic aneurysms (AAA) in 65-year old males is cost-effective at prevalence of about 1%. Since some events occur also in females and among the youngers, screening could be feasible among those at higher risk, such as smokers or individuals with a family history of AAA. The RoCAV (Risk of Cardiovascular diseases and abdominal aortic Aneurysms in Varese) Project is a population-based study aimed to evaluate AAA prevalence in Northern Italy in males over-65 years as well as among females and younger males, and to identify new markers for risk stratification by collecting a large set of CVD risk factors. The aims of the project are: (i) cross-sectional evaluation of AAA prevalence (ii); evaluation of standard CVD risk score as criteria for selecting subgroup at higher risk to be included in a screening program; (iii) identification of new risk markers and risk score algorithm for AAA and CVD risk stratification; (iv) cost-effective evaluation during the follow-up. METHODS: Males aged 50-75 years and females aged 60-75 years, resident in the city of Varese (Lombardy Region), were randomly selected from the civil registry. Among 5198 successfully invited, 3777 subjects accepted to participate and were finally recruited (participation rate 63.8%) from June 2013 to May 2016. Trained operators administered a computerized anamnestic questionnaire, measured anthropometric parameters (BMI, body circumferences, skinfolds), blood pressure, ankle-brachial index, pulse wave velocity and performed abdominal aortic ultrasound scan, ECG and spirometry. All methods were internationally validated. A blood sample was collected and stored in biobank. A follow-up will be carried out through linkage with electronic records. DISCUSSION: Participation rate and data quality assessment were as expected and will reasonably allow to reach the project aims. The expected impact in public health of the RoCAV project will be the potential implementation of a AAA screening program to the whole region as well as the formulation of new criteria for risk assessment of AAA and CVD.

Workplace drug testing on urine samples: evidence for improving efficacy of a first-level screening programme.

BACKGROUND: Previous reports revealed poor performance in identifying drugs of abuse users through first-level workplace drug testing (WDT), based on urine samples. In a cross-sectional study, we evaluated: (i) the effect of creatinine normalization of drug values from diluted urine samples (creatinine levels ≤ 20 mg/dL) on the prevalence of drug users; (ii) the independent procedure-related predictors of positivity and dilution. METHODS: Workers' urine samples were collected at the workplace or at our certified laboratory between 2008 and 2012. All samples were analysed for drugs of abuse by immuno-enzymatic method in our laboratory, according to the Italian WDT law. Detectable drugs of abuse concentrations lower than the positive cutoff values were normalized based on mean levels of urinary creatinine. Detectable concentrations of drugs were confirmed by GC/MS. Multivariate logistic regression was used to detect independent procedure-related predictors of positive and diluted urine samples. RESULTS: Of the 3080 urine samples screened, 51 (1.7%) were found positive for some drugs of abuse (26 cannabinoids and 16 cocaine) and 116 (3.8%) were diluted. Seventeen out of 23 diluted urine samples with detectable concentrations of cannabinoids or cocaine were found positive after urine creatinine normalization and GC/MS confirmed both negative and positive results. This increased the percentage of positivity for cannabinoids and cocaine from 1.35% to 2.09% (+55%, p=0.0005), which is closer to the expected prevalence of drug users based on Italian self-reported surveys. Collection of samples in the laboratory was an independent predictor of positivity (OR=2.33, 95%CI 1.27-4.28) and diluted urine sample (OR=1.65, 95%CI 1.04-2.61). CONCLUSIONS: Efficacy of first-level WDT could be improved by well-controlled pre-analytical procedures and urine creatinine normalization of detected concentrations of drugs of abuse.

Improving long-term prediction of first cardiovascular event: the contribution of family history of coronary heart disease and social status.

OBJECTIVE: The aim of this study is to assess whether family history of coronary heart disease (CHD) and education as proxy of social status improve long-term cardiovascular disease risk prediction in a low-incidence European population. METHODS: The 20-year risk of first coronary or ischemic stroke events was estimated using sex-specific Cox models in 3956 participants of three population-based surveys in northern Italy, aged 35-69 years and free of cardiovascular disease at enrollment. The additional contribution of education and positive family history of CHD was defined as change in discrimination and Net Reclassification Improvement (NRI) over the model including 7 traditional risk factors. RESULTS: Kaplan-Meier 20-year risk was 16.8% in men (254 events) and 6.4% in women (102 events). Low education (hazard ratio=1.35, 95%CI 0.98-1.85) and family history of CHD (1.55; 1.19-2.03) were associated with the endpoint in men, but not in women. In men, the addition of education and family history significantly improved discrimination by 1%; NRI was 6% (95%CI: 0.2%-15.2%), raising to 20% (0.5%-44%) in those at intermediate risk. NRI in women at intermediate risk was 7%. CONCLUSION: In low-incidence populations, family history of CHD and education, easily assessed in clinical practice, should be included in long-term cardiovascular disease risk scores, at least in men.

[Looking for "lost occupational cancers": a systematic evaluation of occupational exposure in a case series of cutaneous squamous cell carcinomas in Italy]. / Alla ricerca dei "tumori professionali perduti": valutazione sistematica dell'esposizione professionale in una serie consecutiva di carcinomi cutanei spinocellulari.

BACKGROUND: Cutaneous carcinomas are tumors with a potential occupational etiology due to exposure to established carcinogens such as polycyclic aromatic hydrocarbons (PAH), ionizing radiation, ultraviolet (UV) radiation and arsenic. The occupational origin of such neoplasms is hugely underestimated in Italy. OBJECTIVES: To asses the proportion of Squamous Cell Carcinomas (SCC) cases with a previous occupational exposure to carcinogens. METHODS: We systematically evaluated occupational exposure in a series of consecutive cases, discharged in the period 2010-11 from the Dermatology Unit of Varese Hospital, Italy, with a histological diagnosis of SCC. Through a structured telephone interview we identified patients with a potential exposure to skin carcinogens. As a second-level step, an extensive evaluation by an occupational physician was performed to assess the occupational etiology in those selected cases. RESULTS: 105 patients were identified (65 men). 15 male cases out of a total of 85 patients who did the telephone interview, revealed a potential occupational exposure; 7 cases were confirmed as occupational cancers after second-level evaluation (proportion of male occupational cases = 13.2%). UV radiation and PAH were recognized as major causal agents. Applying those results to the national incidence data, we estimated a number of 700 annual occupational cases, 100-fold more than the cases currently evaluated by the Italian National Workers Compensation Authority. CONCLUSIONS: Our results revealed that occupational SCC is still at present a substantially "lost disease" in Italy. Greater attention and enhanced collaboration between specialists is thus needed to overcome this tendency.

Prevalence of occupational hazards in patients with different types of epithelial sinonasal cancers.

BACKGROUND: Occupational exposure to carcinogens contributes greatly to the etiology of sinonasal cancer (SNC), but the role of different risk factors in determining different histological subtypes is disputed. METHODOLOGY: All consecutive surgical epithelial SNC cases (case-series study) underwent a systematic occupational medicine examination to determine previous exposure to a wide range of work-related chemical hazards. RESULTS: We investigated 65 SNC cases including intestinal-type adenocarcinoma [ITAC] squamous-cell carcinoma [SCC], and others. Occupational exposure was recognized for 39 cases. Occupational exposures were sensibly more frequent among ITAC than among SCC or other histotypes. Occupational exposure in ITAC cases was to leather or wood dust only, while among non-ITAC cases, we recognised exposure to formaldehyde, solvents and metal fumes. A high proportion of SNC with occupational exposure originated in the ethmoidal epithelium. CONCLUSION: In our case-series of SNC, a very high frequency of previous occupational exposure to carcinogens was detected, suggesting that occupational hazards may be associated to the aetiopathogenesis, primarily for ITAC, but also for other histotypes. Besides leather or wood, other chemical agents must be recognized as occupational risk factors.

Fitness for work in health care workers: state of the art and possible operational recommendations for its formulation and management in relationship to alcohol and drug addiction.

Both chronic and acute alcohol or drug consumption have severe health consequences, alter the subject's cognitive functions and work performance and increase the risk of work-related accidents, for the worker and for third parties (e.g., co-workers and other people subject to negative impact of worker's actions). Limited scientific evidence has suggested that some working conditions present in the health care sector (e.g., high levels of responsibility, competitiveness, burnout, shiftwork, work-related stress) may favour alcohol and drug abuse. The aim of the present report is to describe the problem of alcohol and drug consumption among health care professionals and to evaluate the problem of related fitness for work. The magnitude of this problem remains unclear; recent estimates have reported alcohol abuse and addiction problems in 1-14% and psychotropic, illicit and non-illicit, substance abuse in 6-15% of health care workers. The prevalence of tranquilizer and sedative/hypnotic drug use is high, particularly among physicians. However, it remains unclear whether the incidence of workplace accidents and injuries is higher among drug abusers, and whether the statutory introduction of prevention programmes has led to actual control of this problem in the workplace. Italian legislation identifies the occupational physician as a key figure to prevent psychotropic substance abuse in some work activities, but some difficulties in its application remain. Legislators should issue simple norms that clearly define the responsibilities and skills of each actor involved in safeguarding workplace health and safety, as well as clearly outlining workplace monitoring procedures.

Temporal trends in ischemic and hemorrhagic strokes in Northern Italy: results from the cardiovascular monitoring unit in Northern Italy population-based register, 1998-2004.

BACKGROUND: We compared rates and case fatality from a population-based stroke register in Northern Italy between 1998 and 2004 to assess changes over time and to evaluate changes in case diagnosis and management. METHODS: The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease criteria were used to identify suspected fatal or nonfatal events occurring among residents 35-74 years of age. Data on in-hospital treatments, symptoms and diagnostic tools were extracted. Out-of-hospital deaths were also investigated. The annual average relative change (ARC) in death rate, attack rate and case fatality were derived from Poisson models. RESULTS: Death rates due to ischemic stroke (IS) decreased [men: ARC -12.7, 95% confidence interval (CI) -21.3 to -3.2; women: ARC -14.0, 95% CI -23.3 to -3.5]. These reductions are attributable to decreases in case fatality; attack rates of nonfatal IS increased (men: ARC 3.6, 95% CI 0.5-6.7; women: ARC 4.1, 95% CI 0.0-8.2). IS patients showed a higher prevalence of dyslipidemia and hypertension and underwent MRI more frequently in 2004. Both findings may explain the increased proportions of less severe cases. Case fatality and attack rates for hemorrhagic strokes (HS) were stable, with an observed increased prevalence of patients under anticoagulant/antiplatelet treatments. CONCLUSIONS: In this low-IS-incidence population, death rates decreased substantially during the investigated period. More accurate diagnostic tools increase the probability of detecting less severe cases. HS remains a frequently fatal disease with a stable incidence.

[Prospectic evaluation of the Italian Workers' Compensation Authority in a large case series of Occupational sino-nasal cancers]. / Studio prospettico sulla valutazione in sede INAIL di un'ampia sistica di TuNS professionali.

Sino-nasal cancer (SNC) are rare tumours with an elevated occupational etiological fraction, due both to well-established risk factors (wood and leather) and to more rare carcinogens. We evaluated the assessment for workers' compensation performed by the Italian Authority (INAL) in a case-series of occupational SNC (N = 45). We observed an elevated proportion of cases that were recognised as occupational, overall (36 on 39) and for any histotype. INAIL tended to recognize as professional not only patients with exposure to wood and leather but also cases with a documented exposure to formaldehyde, metal, polycyclic hydrocarbons. Significant differences across Italian macro-regions appeared, when the amount of worker compensation was investigated.

[Psychotropic substances and driving]. / Sostanze psicotrope e guida.

Consumption of psychotropic substances (alcohol, drugs, medication) has a major impact on complex activity performance such as driving. This issue is of relevant social interest for the high number of potentially involved subjects and the often fatale outcomes, and affects also occupational physicians because of the high number of people whose job is driving. There are still few studies trying to assess the presence of a possible association between increased risk of accident/injury at work and consumption of psychotropic substances and results are not always in agreement. In spite of such uncertainties and some Italian regulations still worth being amended by Legislator, the possible impact of consumption of psychoactive substances on driving is an issue to be still better defined for which occupational physicians may play a basic role in the field of prevention, clinics and rehabilitation.

[Job strain and cardiovascular diseases: epidemiologic evidence and prevention]. / Job strain e malattie cardiovascolari: evidenze epidemiologiche e prevenzione.

The present contribution wishes to draw attention to major evidences from more recent studies on the relationship between job strain (JS) and cardiovascular diseases (CVD). In particular the demand-control model and the effort-reward imbalance models will be reviewed. Different outcomes are considered: first hypertension, second coronary heart disease (CHD), third atherosclerosis progression, and finally stroke. All these results are in favor of the association between JS and CVD, but with relevant discrepancies in different socio-cultural contest, in different gender groups, indifferent socio-occupational strata. A recent meta-analysis considering prospective cohort studies attribute to people with high JS a 50% increment in risk of CHD in men. Evidences are scares per women. Many limitations in study design contributes to explain some of the discrepancies in the results obtained so far. Promising first results have been reported for studies exploring the interaction between JS and genetic connotes on blood pressure values. More researchers are needed. Based on the actually available evidences, it is time anyhow to start promotion activities at the workplace to improve Individual coping as well as improve the work climate, contrasting major stressor related to work organization and relationships.

[Job strain and heart rate variability. New evidence and new prospects]. / Job strain e heart rate variability. Nuove evidenze e nuove prospettive.

Work stress has been associated with an increased risk for cardiovascular disease. Two major pathways capable to explain the link between job stress and the cardiovascular diseases have been extensively studied: the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). The analysis of heart rate variability (HRV) has been proposed to assess the regulation of the ANS. Several studies established that HRV reduction is a strong and independent predictor of mortality in patients with various cardiovascular diseases. However the assessment of HRV can also be used as a non-invasive tool to predict cardiovascular events in healthy subjects. The aim of this paper is to review and report the results of main studies assessing the association between JS and HRV. Up to now a limited number of studies assessing the relationship between working conditions and HRV has been published. In the majority of them, higher levels of JS has been found associated with lower values of HRV. The literature suggests that HRV analysis can be a valid indicator of JS effects on the cardiovascular system. For the future studies are necessary longitudinal cohorts studies appropriately selected, to obtain information about the cardiovascular effects of prolonged JS.

[Time trends of incidence rates of work accident with blood contamination in a North Italian teaching hospital]. / Ana+lisi dei trend temporali (2004-11) dei tassi di infortunio biologico in un ospedale universitario del nord Italia. Quali evidenze di efficacia dei sistemi di prelievo a vuoto?

Unbiased estimates of incidence rates of accidents with blood contaminations (ABC) and time trends is the milieu for assessing the effectiveness of preventive interventions. A standardised procedure for registration and follow-up of ABC was et up in a North Italian hospital since 2002. Accurate estimates of rate denominator, as full-time equivalent (FTE) person-years, was calculated, for exposed workers only and excluding periods of prolonged absence. In the observation period (2004-2011), training courses for head nurses on security procedures were repeatedly carried out as well as the progressive introduction of vacuum blood collection systems (since 2009). 1287 ABC have been reported, corresponding to an overall annual crude incidence rate of 4.73 per 100 FTE. Temporal trends, calculated on the biennial incidence, resulted in a reductions over the time period considered, in particular for needlestick injuries. Our results support the notions on the efficacy of the adopted prevention measures.

[Workplace health promotion: what evidence of effectiveness?]. / Promozione della salute negli ambienti di lavoro: quali evidenze di efficacia?

Workplace health promotion is a strategy that takes in consideration the synergic effects of behavioural and professional health risks. The workplace can help to improve workers' lifestyles, based on specific programmes conducted by trained occupational physicians. In this article we report on the conclusions of two recent reviews, assessing the evidences of effectiveness of workplace health promotion (WHP) programs, recently published. Even if most of the studies are influenced by methodological concerns and limitations, above all the lack of control groups and the use of multiple and heterogenic outcome measures, it is possible to conclude that health assessment programmes with feedbacks are capable to reduce the risks of alcohol abuse, to increase smoking cessation and to improve levels of physical activity in voluntarily recruited employs. Finally, preliminary indications of the SIMLII Workplace Health Promotion Guidelines are briefly commented.

Shift work and pregnancy outcomes: a systematic review with meta-analysis of currently available epidemiological studies.

BACKGROUND: Varying work schedules are suspected of increasing risks to pregnant women and to fetal wellbeing. In particular, maternal hormonal disturbance arising from sleep deprivation or circadian rhythm disruption might impair fetal growth or lead to complications of pregnancy. Two independent meta-analyses (from 2000 to 2007) reported a small adverse effect of shift work on the risk of preterm delivery (PTD). However, these reviews were based on few high-quality studies. OBJECTIVES: To provide an updated review of the associations of shift work with PTD, low birthweight (LBW), small-for-gestational-age (SGA) infants and pre-eclampsia. SEARCH STRATEGY AND SELECTION CRITERIA: We conducted a systematic search of MEDLINE using combinations of keywords and MeSH terms. DATA COLLECTION AND ANALYSIS: For each relevant paper we abstracted standard details, used to summarise design features and rate methodological quality. We calculated pooled estimates of relative risk (RR) in random-effect meta-analyses. MAIN RESULTS: We retrieved 23 relevant studies. The pooled estimate of RR for PTD was 1.16 (95% CI 1.00-1.33, 16 studies), but when five reports of poorer methodological quality were excluded, the estimated RR decreased to 1.03 (95% CI 0.93-1.14). We also observed increased RRs for LBW (RR 1.27, 95% CI 0.93-1.74) and for SGA (RR 1.12, 95% CI 1.03-1.22), which varied little by study quality. Little evidence was found on pre-eclampsia. CONCLUSIONS: These findings suggest that overall, any risk of PTD, LBW, or SGA arising from shift work in pregnancy is small.

[Methodological aspects in the evaluation of turn-over and up/down sizing as indicators of work-related stress]. / Aspetti metodologici per la valutazione di turn-over e up/down-sizing quali indicatori di stress da lavoro.

We discuss the methodological aspects related to the evaluation of turn-over and up-down sizing as indicators of work-related stress, in complex organizations like a university hospital. To estimate the active workers population we developed an algorithm which integrated several administrative databases. The indicators were standardized to take into account some potential confounders (age, sex, work seniority) when considering different hospital structures and job mansions. Main advantages of our method include flexibility in the choice of the analysis detail (hospital units, job mansions, a combination of both) and the possibility to describe over-time trends to measure the success of preventive strategies.

[Comparison of the training schemes of the specialization schools of the public health area: a rational basis for a proposal of a core curriculum for the university training programme contained in article 38 of Legislative Decree (D.Lgs) 81/2008]. / Confronto dei contenuti formativi delle scuole di specializzazione dell'Area di Sanità Pubblica: le basi razionali per una proposta di core curriculum per il percorso formativo universitario ex art. 38, D.Lgs 81/2008.

A document by the B. Ramazzini College of University Teachers of Occupational Medicine of the Italian Society of Occupational Health and Industrial Hygiene (S.I.M.L.I.I). The aim of this document was to compare the professional competence, training profile and core curricula of the three main specialization courses in the Public Health postgraduate medical area, i.e., Occupational Medicine, Hygiene and Preventive Medicine, and Forensic Medicine, such as contained in the Ministerial Decree (D.M) of 1 August 2005. We set out to identify, using clear and objective criteria, the knowledge and skills that specialists in Hygiene or Forensic Medicine must develop, in accordance with Art. 38 of the new Italian law on safety ahd health at work (D.Lgs 81/2008), in order to be authorized to perform occupational health activities as "Competent Physicians" (CP). The comparison revealed significant differences in structure and content among the three courses. In particular, compared to the course in Occupational Medicine, the courses in Hygiene and in Forensic Medicine both lack clinical training, including diagnostic and therapeutic skills, risk-oriented occupational health activities, biological monitoring, assessment of individual susceptibility, and clinical or instrumental procedures to prevent and detect occupational diseases. Furthermore, the specialization course in Hygiene lacks any training regarding the criteria and methods for assessing the individual worker's fitness for work, while the course in Forensic Medicine lacks any training in occupational risk assessment and management. From this comparison, a list was derived of the education and training debits that specialists in Hygiene or Forensic Medicine should cover (credits) in order to be authorized to perform CP activities as indicated by the new law. A core curriculum is proposed here, based on the corresponding credits, for use as a reference.

[Heart disease and work: from rehabilitation to return to work]. / Cardiopatie e lavoro: dalla riabilitazione al reinserimento lavorativo.

Cardiovascular disease is one of the main causes of death and disability in industrialised and post-industrialised countries, including Italy. Improvements in treatment of the acute phase and the efficacy of prevention programmes contribute greatly to extending patient survival, thus increasing the prevalence of the disease even in the population of working age. Thus it is mandatory to provide adequate rehabilitation programmes in order to achieve full social reintegration of such patients, including return to work, which is an important aspect of their quality of life. This report reviews published papers exploring the main factors influencing return to work of patients suffering from a heart complaint. Criteria are also proposed for the assessment of reintegration at work of cardiovascular patients that take account of the residual clinical and functional working capacity of the patient in relation to the specific environmental and organizational work features. With the tools available to monitor the cardiovascular system during work it is possible to pursue to advantage such a comprehensive rehabilitation programme but close cooperation between the occupational physicians and cardiovascular rehabilitation specialists is required In a preliminary phase this can be achieved in hospital outpatient clinics equipped to develop and test specific protocols.

[Drug use among workers: an update]. / Aggiornamenti in tema di abuso di sostanze stupefacenti e psicotrope.

We present data coming from two years of surveillance of drug use among workers, as provided for by the recent law. Urine samples have been collected either by our lab or by the firm; procedures and investigated substances followed the law. Self-reported information on job duties and history of drug use have also been collected. Between September 2008 and April 2010, n = 2745 workers (age 40.5 +/- 9.5, 98% men, 43% handling workers) were screened, for a total number of 3002 urine samples. Among the samples with creatinine > = 20 mg/dl (n = 2878), 46 were positive (1.6%); no temporal trends were detected. Cannabis e cocaine were the two most spread substances. Positivity was associated with young age and presence of another positive sample in the same firm. Furthermore, we present the results of the analysis (urine and hair samples) on 146 suspected drug abuser selected by the SERT Varese in the same time period.