ObjectiveTo determine burn-out levels and associated factors among healthcare personnel working in a tertiary hospital of a highly burdened area of north-east Italy during the COVID-19 pandemic.DesignObservational study conducted from 21 April to 6 May 2020 using a web-based questionnaire.SettingResearch conducted in the Verona University Hospital (Veneto, Italy).ParticipantsOut of 2195 eligible participants, 1961 healthcare workers with the full range of professional profiles (89.3%) completed the survey.Primary outcome measureLevels of burn-out, assessed by the Maslach Burnout Inventory-General Survey (MBI-GS). Multivariable logistic regression analysis was performed to identify factors associated with burn-out in each MBI-GS dimension (emotional exhaustion, EX; professional efficacy, EF; cynicism, CY).ResultsOverall, 38.3% displayed high EX, 46.5% low EF and 26.5% high CY. Burn-out was frequent among staff working in intensive care units (EX 57.0%; EF 47.8%; CY 40.1%), and among residents (EX 34.9%; EF 63.9%; CY 33.4%) and nurses (EX 49.2%; EF 46.9%; CY 29.7%). Being a resident increased the risk of burn-out (by nearly 2.5 times) in all the three MBI subscales and being a nurse increased the risk of burn-out in the EX dimension in comparison to physicians. Healthcare staff directly engaged with patients with COVID-19 showed more EX and CY than those working in non-COVID wards. Finally, the risk of burn-out was higher in staff showing pre-existing psychological problems, in those having experienced a COVID-related traumatic event and in those having experienced interpersonal avoidance in the workplace and personal life.ConclusionsBurn-out represents a great concern for healthcare staff working in a large tertiary hospital during the COVID-19 pandemic and its impact is more burdensome for front-line junior physicians. This study underlines the need to carefully address psychological well-being of healthcare workers to prevent the increase of burn-out in the event of a new COVID-19 healthcare emergency.

Aims Healthcare workers exposed to coronavirus 2019 (COVID-19) patients could be psychologically distressed. This study aims to assess the magnitude of psychological distress and associated factors among hospital staff during the COVID-19 pandemic in a large tertiary hospital located in north-east Italy. Methods All healthcare and administrative staff working in the Verona University Hospital (Veneto, Italy) during the COVID-19 pandemic were asked to complete a web-based survey from 21 April to 6 May 2020. Symptoms of post-traumatic distress, anxiety and depression were assessed, respectively, using the Impact of Event Scale (IES-R), the Self-rating Anxiety Scale (SAS) and the Patient Health Questionnaire (PHQ-9). Personal socio-demographic information and job characteristics were also collected, including gender, age, living condition, having pre-existing psychological problems, occupation, length of working experience, hospital unit (ICUs and sub-intensive COVID-19 units vs. non-COVID-19 units). A multivariable logistic regression analysis was performed to identify factors associated with each of the three mental health outcomes. Results A total of 2195 healthcare workers (36.9% of the overall hospital staff) participated in the study. Of the participants, 35.7% were nurses, 24.3% other healthcare staff, 16.4% residents, 13.9% physicians and 9.7% administrative staff. Nine per cent of healthcare staff worked in ICUs, 8% in sub-intensive COVID-19 units and 7.6% in other front-line services, while the remaining staff worked in hospital units not directly engaged with COVID-19 patients. Overall, 63.2% of participants reported COVID-related traumatic experiences at work and 53.8% (95% CI 51.0%–56.6%) showed symptoms of post-traumatic distress; moreover, 50.1% (95% CI 47.9%–52.3%) showed symptoms of clinically relevant anxiety and 26.6% (95% CI 24.7%–28.5%) symptoms of at least moderate depression. Multivariable logistic regressions showed that women, nurses, healthcare workers directly engaged with COVID-19 patients and those with pre-existing psychological problems were at increased risk of psychopathological consequences of the pandemic. Conclusions The psychological impact of the COVID-19 pandemic on healthcare staff working in a highly burdened geographical of north-east Italy is relevant and to some extent greater than that reported in China. The study provides solid grounds to elaborate and implement interventions pertaining to psychology and occupational health.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Tobacco smoking and occupation are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Glutathione S-transferase (GST) M1, T1 and P1 are involved in the detoxification of PAH reactive metabolites. Two N-acetyltransferase isozymes, NAT2 and NAT1, have major roles in catalyzing the N-acetylation and O-acetylation of aromatic amines. Cytochrome P450 1B1 (CYP1B1) and sulfotransferase 1A1 (SULT1A1) are also involved in the metabolism of PAHs and aromatic amines. It is hypothesized that the genetic polymorphisms of these metabolic enzymes have an effect on the individual susceptibility to bladder cancer in particular by interacting with relevant environmental exposures. A hospital-based case-control study among men in Brescia, Northern Italy recruited 201 incidence cases and 214 controls from 1997-2000. Occupational exposures were blindly coded by occupational physicians. Genotyping of polymorphisms were carried out with PCR-RFLP method. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk. Effect modifications by age of onset, smoking and occupational exposures to PAHs and aromatic amines were evaluated. We also conducted an analysis of interaction between genetic factors. GSTM1 and GSTT1 null genotype were associated with an increased risk of bladder cancer with an odds ratio (OR) of 1.69 (95% confidence interval [CI] ‫؍‬ 1.11-2.56) and 1.74 (95% CI ‫؍‬ 1.02-2.95), respectively. The effect of GSTM1 null was seen particularly in heavy smokers, and there was a combined effect with occupational exposure of aromatic amines (OR ‫؍‬ 2.77, 95% CI ‫؍‬ 1.08 -7.10). We observed a trend (p-value < 0.01) of increasing cancer risk comparing subjects with normal GSTM1 and T1 activity to subjects with one (OR ‫؍‬ 1.82, 95% CI ‫؍‬ 1.16 -2.85) or both null genotypes (OR ‫؍‬ 2.58, 95% CI ‫؍‬ 1.27-5.23). NAT2 slow acetylator was associated with marginally increased risk of bladder cancer (OR ‫؍‬ 1.50, 95% CI ‫؍‬ 0.99 -2.27), and the OR for the joint effect with occupational exposure of aromatic amines was 3.26 (95% CI ‫؍‬ 1.06 -9.95). SULT1A1 Arg213His polymorphism showed a marginal protective effect. These findings suggest that individual susceptibility to bladder cancer may be modulated by GSTM1, GSTT1 and NAT2 polymorphisms.

Tobacco smoking and occupational exposure are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines, which lead to oxidative stress and DNA damage. Several enzymes, which play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase (MPO) produces a strong oxidant for microbicidal activity, and activates carcinogens in tobacco smoke. Catechol-O-methyltransferase (COMT) catalyzes the methylation of endo- and xenobiotics and prevents redox cycling. NAD(P)H:quinone oxidoreductase (NQO1) catalyzes the two-electron reduction of quinoid compounds, which also protects cells from redox cycling. Manganese superoxide dismutase (MnSOD) protects cells from free radical injury. To test the hypothesis that the risk of bladder cancer can be influenced by polymorphisms in the genes that modulate oxidative stress, in particular by interacting with environmental carcinogens, we conducted a hospital-based case-control study among men in Brescia, Northern Italy. We recruited and interviewed 201 incident cases and 214 controls from 1997 to 2000. Occupational exposures to PAHs and aromatic amines were coded blindly by occupational physicians. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk and the effect of modifications of smoking and occupational exposures were evaluated. MPO G-463A homozygous variant was associated with a reduced risk of bladder cancer with an OR of 0.31 (95% CI = 0.12-0.80). MnSOD Val/Val genotype increased the risk of bladder cancer with OR of 1.91 (95% CI = 1.20-3.04), and there was a combined effect with smoking (OR = 7.20, 95% CI = 3.23-16.1) and PAH (OR = 3.02, 95% CI = 1.35-6.74). We did not observe an effect of COMT Val108Met polymorphism. These findings suggest that individual susceptibility of bladder cancer may be modulated by MPO and MnSOD polymorphisms, and that the combination of genetic factors involved in oxidative stress response with environmental carcinogens may play an important role in bladder carcinogenesis.

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. [Cancer Res 2009;69(17):6857-64]