Implementation of COVID-19 vaccination services in prison in six European countries: translating emergency intervention into routine life-course vaccination.

BACKGROUND: Evidence has shown that the risk of transmission of SARS-CoV-2 is much higher in prisons than in the community. The release of the COVID-19 vaccine and the recommendation by WHO to include prisons among priority settings have led to the inclusion of prisons in national COVID-19 vaccination strategies. Evidence on prison health and healthcare services provision is limited and often focuses on a single country or institution due to the multiple challenges of conducting research in prison settings. The present study was done in the framework of the EU-founded project RISE-Vac. It aimed to analyse the best practices and challenges applied in implementing COVID-19 universal vaccination services during the pandemic to support future expansion of routine life course vaccination services for people living in prison (PLP). METHODS: Two online cross-sectional surveys were designed and piloted: survey1 on prison characteristics and (non-COVID-19) immunisation practices; survey2 on the implementation and coverage of COVID-19 vaccination with open-ended questions for thematic analysis. Each RISE-Vac project partner distributed the questionnaire to one or two prisons in their country. Answers were collected from eight European prisons' directors or medical directors between November 2021-May 2022. RESULTS: According to our findings, the implementation modalities of COVID-19 vaccination services in the surveyed prisons were effective in improving PLP vaccination coverage. Strategies for optimal management of the vaccination campaign included: periodic time slot for PLP vaccination; new staff recruitment and task shifting; distribution of informational material both to PLP and prison staff. Key challenges included continuity of care after release, immunisation information system, and vaccine hesitancy. CONCLUSIONS: To the best of our knowledge, this is the first study describing the implementation of COVID-19 vaccination services in European prisons, suggesting that the expansion of vaccination provision in prison is possible. There is no unique solution that will fit every country but commonalities likely to be important in the design and implementation of future vaccination campaigns targeting PLP emerged. Increased availability of vaccination services in prison is not only possible, but feasible and highly desirable, and can contribute to the reduction of health inequalities.

BMI and breast cancer risk around age at menopause.

BACKGROUND: A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Response to Ustekinumab Therapy Is Associated with an Improvement of Nutritional Status in Patients with Crohn's Disease.

The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p-value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p-values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.

A prospective study of the association between living in a rural environment during childhood and risk of psoriasis.

Psoriasis is one of the most common immune-mediated inflammatory diseases (IMIDs). Living in a rural environment during childhood is associated with a decreased risk of certain IMIDs, like asthma, in adulthood. However, its role in other IMIDs, such as psoriasis is still unclear. To evaluate the relationships between different factors related to the environment during childhood and the risk of psoriasis in adulthood we conducted a study in E3N, a French prospective cohort composed of 98 995 women. During the 1990-2018 follow-up of 72 154 study participants, we identified 1 967 incident cases of psoriasis from self-reports in self-administered structured questionnaires. During the 2004-2018 follow-up of 67 917 study participants, 188 moderate-to-severe cases of psoriasis were identified through self-reports and from data from a drug reimbursement database. We fitted Cox proportional hazards regression models with age as the time scale from which we estimated hazard ratios adjusted for putative confounders (aHRs). We found inverse associations with risk of psoriasis for rural birthplace [aHR: 0.89 (95%CI: 0.79-0.96)] and for having farming parents [aHR: 0.84 (95%CI: 0.72-0.97)]. For moderate-to-severe psoriasis we found a nominally similar inverse association with rural birthplace but not with having farming parents. Our results suggest that an exposure to a rural environment during childhood may be associated with a reduced risk of psoriasis. These findings may help to improve our understanding of the pathogenesis of psoriasis.

Mediating Role of Lifestyle Behaviors in the Association between Education and Cancer: Results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. METHODS: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). RESULTS: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). CONCLUSIONS: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. IMPACT: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Reorganization of Intensive Care Units for the COVID-19 pandemic: effects on nursing sensitive outcomes.

Background: Since the first months of 2020 COVID-19 patients who were seriously ill due to the development of ARDS, required admission to the intensive care unit to ensure potentially life-saving mechanical ventilation and support for vital functions. To cope with this emergency, an extremely rapid reorganization of premises, services and staff, to dedicate an entire intensive care unit exclusively to SARS-CoV-2 patients and increasing the number of beds was essential. The aim of the study was to evaluate the effects of reorganization of the COVID-19 intensive care unit in terms of nursing sensitive outcomes. Methods: a retrospective observational study was conducted to compare nursing sensitive outcomes between pre-COVID period and COVID period. Results: Falls (0.0 and 0.4%, respectively), physical restraint (1.8 and 1.1%, respectively), and pressure ulcers (8.0 and 3.0%, respectively) were similar in the COVID and in the pre-COVID group. After adjusting for gender, age, BMI, and number of comorbidities, the incidence of bloodstream infections was significantly higher in the COVID group than in the pre-COVID group. There were no statistically significant differences in the incidence between the two groups regarding other evaluated outcomes. Conclusion: The selected nursing sensitive outcomes maintained similar values in the pre-COVID and COVID patient groups. Healthcare-related infections rate must be considered an important alarm signal of quality of nursing care especially in conditions of excessive workload, stress and the presence of less experienced staff increase.

Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies.

BACKGROUND: DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. METHODS: Using data from four prospective case-control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. RESULTS: None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath 'age acceleration' (AA): OR per SD = 1.02, 95%CI: 0.95-1.10; AA-Hannum: OR = 1.03, 95%CI:0.95-1.12; PhenoAge: OR = 1.01, 95%CI: 0.94-1.09 and GrimAge: OR = 1.03, 95%CI: 0.94-1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01-1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. CONCLUSION: We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer.

Vaccine hesitancy and cognitive biases: Evidence for tailored communication with parents.

Background: Vaccine hesitancy (VH) remains worldwide a reason of concern. Most of the vaccination education strategies followed a "fact-based" approach, based on the assumption that decision making is a rational process, without considering the influence of cognitive biases and heuristics. Our study aimed at identifying factors involved in the parents' vaccination choice to inform and shape communication interventions. Methods: We conducted an online national survey among parents between November 2020 and April 2021. The questionnaire consisted of 42 items organised in 4 parts: (1) personal information, (2) cognitive biases and risk propension, (3) Analytic Thinking (Cognitive Reflection Test), (4) conspiracy mentality, health literacy, and VH. Exploratory factor analysis was conducted to identify latent variables underlying the 19 items related to the 6 cognitive biases. Factors were categorised in quintiles and the corresponding pseudo-continuous variables used as predictors of the VH. Logistic regression model was applied to assess the association of the VH with factors, conspiracy mentality and risk propension. We adjusted for age, gender, economic status, and education levels. Results: The study included 939 parents, 764 women (81.4%), 69.8% had a degree or higher level of education. Considering cognitive biases, four factors explaining 54% of the total variance were identified and characterised as: fear of the side effects of vaccines (scepticism factor); carelessness of the risk and consequences of infections (denial factor); optimistic attitude (optimistic bias factor); preference for natural products (naturalness bias factor). All factors were positively associated to VH (p < 0.001) as were conspiracy mentality (p = 0.007) and risk propension (p = 0.002). Conclusions: This study confirmed the need to amplify the model used to analyse the VH considering cognitive biases as important factor affecting the parents' decision making. These results may be useful to design personalised communication interventions regarding vaccines and vaccination.

Impact of low-dose acetylsalicylic acid on pregnancy outcome in systemic lupus erythematosus: results from a multicentre study.

OBJECTIVE: It is still a matter of debate whether low-dose acetylsalicylic acid (LDASA) should be prescribed to all patients with SLE during pregnancy. This study aimed at investigating the impact of LDASA on pregnancy outcomes in patients with SLE without history of renal involvement and without antiphospholipid antibodies (aPL). METHODS: This is a retrospective analysis of prospectively monitored pregnancies at seven rheumatology centres. Previous/current renal involvement and aPL positivity were the exclusion criteria. Adverse pregnancy outcome (APO) is the composite outcome of the study and included proteinuric pre-eclampsia, preterm delivery <37 weeks, small-for-gestational age infant, low birth weight <2500 g, intrauterine growth restriction and intrauterine fetal death after 12 weeks of gestation of a morphologically normal fetus. RESULTS: 216 pregnancies in 187 patients were included; 82 pregnancies (38.0%) were exposed to LDASA treatment. No differences in terms of age at conception, disease duration, clinical manifestations, comorbidities and disease flare during pregnancy were observed between patients taking LDASA and those who did not take LDASA during pregnancy. APO was observed in 65 cases (30.1%), including 13 cases (6.1%) of pre-eclampsia. The incidence of all complications was similar in the two groups. However, it is interesting to note that pre-eclampsia had lower frequency in patients taking LDASA versus those not taking LDASA (2.4% vs 8.3%, p=0.14). CONCLUSIONS: In pregnant patients with SLE without renal involvement and were aPL-negative, there is a low risk of severe obstetric complications, such as early pre-eclampsia. LDASA treatment does not provide a statistically significant advantage over these complications. However, a careful individual risk-benefit balance is warranted.

Use of Biological Drugs for Psoriasis: A Drug-Utilization Study Using Tuscan Administrative Databanks.

Our study aims at providing evidence on patterns of use of biologic drugs for psoriasis in Tuscany, Italy. We conducted a drug-utilization study based on administrative databanks of Tuscany (EUPAS45365) from 2011 to 2019. We selected new users of etanercept, infliximab, adalimumab, ustekinumab, or secukinumab between 1 January 2011 and 31 December 2016. We considered subjects with psoriasis and followed subjects until the end of the study period (three years after the first dispensation of biologic drug for psoriasis) or the patient's death, whichever came first. We censored subjects for pregnancy or neoplasia. For each subject, we defined the state as the weekly coverage of one of the biologic drugs of interest. We then defined the switch as the change from a state to another one. A total of 7062 subjects with a first dispensation of a PSObio drug in the inclusion period was identified, and 1839 (52.9% female, 51.6 mean age) patients were included in the analysis. Among new users of adalimumab (N = 770, 41.9%), one third showed a continuous behaviour whereas the others moved to etanercept and ustekinumab. New users of etanercept (N = 758, 41.2%), had the highest proportion of switchers, with adalimumab most often being the second choice. New users of infliximab (N = 159, 8.6%) experienced the highest proportion of treatment discontinuation. The present study suggests that the majority of patients treated with PSObio drugs do not switch from one active ingredient to another. However, patients who started biological therapy with etanercept had the highest frequency of switching to other PSObio drugs, whereas those who started with secukinumab or ustekinumab had the lowest.

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF, but not vedolizumab.

BACKGROUND: Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD. METHODS: We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54. RESULTS: Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts. CONCLUSION: Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.

COVID-19 Infection Among Incarcerated Individuals and Prison Staff in Lombardy, Italy, March 2020 to February 2021.

Importance: Owing to infrastructural and population characteristics, the prison setting is at increased risk for transmission of SARS-CoV-2 and for severe clinical outcomes. Because of structural and operational reasons, research in prison settings is challenging and available studies are often monocentric and have limited temporal coverage; broader-based research is necessary. Objectives: To assess the extent and dynamics of the COVID-19 pandemic within the prison system of a large Italian region, Lombardy, and report the infection prevention and control measures implemented. Design, Setting, and Participants: This repeated cross-sectional study was carried out from March 1, 2020, through February 28, 2021 (first wave, March-June 2020; second wave, October 2020-February 2021) in the prison system of Lombardy, which includes 18 detention facilities for adults. All incarcerated persons and the prison staff of the penitentiary system of the Lombardy region participated in the study. Exposures: The main exposures of interest were the weekly average number of incarcerated individuals placed in quarantine in single or shared isolation rooms, the rate of sick leave by symptomatic and asymptomatic prison staff reported to the prison occupational medicine department on a weekly basis, and the level of overcrowding. Main Outcomes and Measures: The primary outcome measures were weekly COVID-19 crude case rates, weekly test positivity rate, and the relative risk of acquiring the infection for prison staff, incarcerated persons, and the general population. Results: The study population comprised a mean of 7599 incarcerated individuals and 4591 prison staff. Approximately 5.1% of the prison population were women; demographic characteristics of the prison staff were not available. During the study, COVID-19 occurred in 1564 incarcerated individuals and 661 prison staff. Most of these cases were reported during the second wave (1474 in incarcerated individuals, 529 in prison staff), when stringent measures previously enforced were relaxed. During both epidemic waves, incarcerated individuals and prison staff had a higher relative risk for COVID-19 infection than the general population during both the first wave (incarcerated individuals: 1.30; 95% CI, 1.06-1.58; prison staff: 3.23; 95% CI, 2.74-3.84) and the second wave (incarcerated individuals: 3.91; 95% CI, 3.73-4.09; prison staff: 2.61; 95% CI, 2.41-2.82). Conclusions and Relevance: The findings of this study suggest that the prison setting was an element of fragility during COVID-19 pandemic, with a high burden of COVID-19 cases among both the incarcerated individuals and prison staff. The prison setting and prison population need to be included and possibly prioritized in the response during epidemic events.

Can the computed tomography texture analysis of colorectal liver metastases predict the response to first-line cytotoxic chemotherapy?

BACKGROUND: Artificial intelligence in radiology has the potential to assist with the diagnosis, prognostication and therapeutic response prediction of various cancers. A few studies have reported that texture analysis can be helpful in predicting the response to chemotherapy for colorectal liver metastases, however, the results have varied. Necrotic metastases were not clearly excluded in these studies and in most studies the full range of texture analysis features were not evaluated. This study was designed to determine if the computed tomography (CT) texture analysis results of non-necrotic colorectal liver metastases differ from previous reports. A larger range of texture features were also evaluated to identify potential new biomarkers. AIM: To identify potential new imaging biomarkers with CT texture analysis which can predict the response to first-line cytotoxic chemotherapy in non-necrotic colorectal liver metastases (CRLMs). METHODS: Patients who presented with CRLMs from 2012 to 2020 were retrospectively selected on the institutional radiology information system of our private radiology practice. The inclusion criteria were non-necrotic CRLMs with a minimum size of 10 mm (diagnosed on archived 1.25 mm portal venous phase CT scans) which were treated with standard first-line cytotoxic chemotherapy (FOLFOX, FOLFIRI, FOLFOXIRI, CAPE-OX, CAPE-IRI or capecitabine). The final study cohort consisted of 29 patients. The treatment response of the CRLMs was classified according to the RECIST 1.1 criteria. By means of CT texture analysis, various first and second order texture features were extracted from a single non-necrotic target CRLM in each responding and non-responding patient. Associations between features and response to chemotherapy were assessed by logistic regression models. The prognostic accuracy of selected features was evaluated by using the area under the curve. RESULTS: There were 15 responders (partial response) and 14 non-responders (7 stable and 7 with progressive disease). The responders presented with a higher number of CRLMs (P = 0.05). In univariable analysis, eight texture features of the responding CRLMs were associated with treatment response, but due to strong correlations among some of the features, only two features, namely minimum histogram gradient intensity and long run low grey level emphasis, were included in the multiple analysis. The area under the receiver operating characteristic curve of the multiple model was 0.80 (95%CI: 0.64 to 0.96), with a sensitivity of 0.73 (95%CI: 0.48 to 0.89) and a specificity of 0.79 (95%CI: 0.52 to 0.92). CONCLUSION: Eight first and second order texture features, but particularly minimum histogram gradient intensity and long run low grey level emphasis are significantly correlated with treatment response in non-necrotic CRLMs.

Associations between plasma levels of brominated flame retardants and methylation of DNA from peripheral blood: A cross-sectional study in a cohort of French women.

BACKGROUND: Brominated flame retardants (BFRs) are organic compounds that are widespread in the environment. Because of their persistence, they are able to bioaccumulate with major impacts on human health. It has been hypothesized that the effect of BFRs on human health is mediated by alterations of DNA methylation. OBJECTIVE: The aim of this study was to examine the association between methylation of DNA extracted from peripheral blood and circulating levels of BFRs measured in plasma. METHODS: We conducted a methylation wide association study on 336 blood samples from a study within the E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort, a long-term longitudinal cohort of French women. DNA methylation at more than 850 000 cytosine-guanine dinucleotide (CpG) sites was measured with the Illumina Infinium HumanMethylation - EPIC BeadChip. Circulating levels of seven BFRs (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154 and PBB-153) were measured by gas chromatography coupled to high-resolution mass spectrometry in plasma samples. The association between DNA methylation and BFRs plasma levels was assessed through linear mixed-effects models followed by gene-set enrichment analyses (GSEA). RESULTS: We identified 253 CpG sites whose methylation levels were significantly associated with exposure to BFRs after Bonferroni correction. For 50 of these CpGs the p-values were less than 2.2x10-9 with the strongest association being between BDE-154 and cg23619365 (4.32x10-13). GSEA of CpG sites associated with exposure to BFRs identified significant enrichment of genes involved in hypoxia, glycolysis and adipogenesis. CONCLUSIONS: Exposure to BFRs appears to be related to numerous alterations in DNA methylation. These findings, if replicated in independent studies, provide insights into the biological and health effects of BFRs.

Myeloid neoplasms and autoimmune diseases: markers of association.

OBJECTIVES: To investigate the prognostic significance of concomitant autoimmune diseases (ADs) in myeloproliferative neoplasms (MPNs). METHODS: 435 subjects with a diagnosis of MPNs were included in this observational single institution longitudinal study. Of them, 34 patients presented an overt AD at diagnosis of MPN. Clinical presenting features, progression-free and overall survival were compared between MPN subgroups in relation to co-existence of AD at diagnosis of MPN. RESULTS: Compared to cases without ADs, the subjects with ADs were significantly younger, had lower haemoglobin and haematocrit levels and more frequently presented with splenomegaly. The clinical and biological features associated to progression-free and overall survival were: age, presence of splenomegaly, histotype (MF vs. PV vs. ET), anaemia, high platelet count and presence of any AD at diagnosis of MPN. The age-adjusted hazard ratio (HR) of progression for the presence of AD at diagnosis of MPN was 2.76. Overall survival was not significantly associated to AD at diagnosis, but the HR of progression for the presence of AD at diagnosis of MPN was 2.18. CONCLUSIONS: A possible common genetic predisposition, the inflammatory bone marrow microenvironment and the activation of theJAK/STAT pathway could be considered as responsible for the observed association between MPNs and ADs.

Trajectories of Adherence to Biologic Disease-Modifying Anti-Rheumatic Drugs in Tuscan Administrative Databases: The Pathfinder Study.

Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.

Association between telomere length and mitochondrial copy number and cancer risk in humans: A meta-analysis on more than 300,000 individuals.

In the last decades the association of leukocyte telomere length (LTL) and mitochondrial copy number (mtDNAcn) with cancer risk has been the focus of many reports, however the relation is not yet completely understood. A meta-analysis of 112 studies including 64,184 cancer cases and 278,641 controls that analysed LTL and mtDNAcn in relation to cancer risk has been conducted to further our understanding of the topic. Stratified analyses for tumor type were also performed. Overall, no association was observed for all cancer combined neither for LTL nor mtDNAcn. Significant associations were detected for these biomarkers and specific cancer type; however, a large degree of heterogeneity was present, even within the same tumor type. Alternatives approaches based on polymorphic variants, such as polygenic risk scores and mendelian randomization, could be adopted to unravel the causal correlation of telomere length and mitochondrial copy number with cancer risk.

Telomere Length and Male Fertility.

Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2-rs11125529 and decreased sperm motility (p = 0.03); PXK-rs6772228 with a lower sperm count (p = 0.02); NAF1-rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208-rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.

Psychological distress in the academic population and its association with socio-demographic and lifestyle characteristics during COVID-19 pandemic lockdown: Results from a large multicenter Italian study.

Measures implemented in many countries to contain the COVID-19 pandemic resulted in a change in lifestyle with unpredictable consequences on physical and mental health. We aimed at identifying the variables associated with psychological distress during the lockdown between April and May 2020 in the Italian academic population. We conducted a multicenter cross-sectional online survey (IO CONTO 2020) within five Italian universities. Among about 240,000 individuals invited to participate through institutional communications, 18 120 filled the questionnaire. Psychological distress was measured by the self-administered Hospital Anxiety and Depression Scale (HADS). The covariates collected included demographic and lifestyle characteristics, trust in government, doctors and scientists. Associations of covariates with influenza-like symptoms or positive COVID-19 test and with psychological distress were assessed by multiple regression models at the local level; a meta-analysis of the results was then performed. Severe levels of anxiety or depression were reported by 20% of the sample and were associated with being a student or having a lower income, irrespective of their health condition and worries about contracting the virus. The probability of being severely anxious or depressed also depended on physical activity: compared to those never exercising, the highest OR being for those who stopped during lockdown (1.53; 95% CI, 1.28 to 1.84) and the lowest for those who continued (0.78; 95% CI, 0.64 to 0.95). Up to 21% of severe cases of anxiety or depression might have been avoided if during lockdown participants had continued to exercise as before. Socioeconomic insecurity contributes to increase mental problems related to the COVID-19 pandemic and to the measures to contain it. Maintaining or introducing an adequate level of physical activity is likely to mitigate such detrimental effects. Promoting safe practice of physical activity should remain a public health priority to reduce health risks during the pandemic.