Background: The association between air pollution and green spaces with breast cancer risk stratified by menopausal status has not been frequently investigated despite its importance given the different impact of risk factors on breast cancer risk depending on menopausal status. Objectives: To study the association between air pollution, green spaces and pre and postmenopausal breast cancer risk. Methods: We conducted a population-based cohort study using electronic primary care records in Catalonia. We included women aged 17-85 years free of cancer at study entry between 2009 and 2017. Our exposures were particulate matter < 2.5 mu m (PM2.5) & < 10 mu m (PM10), nitrogen dioxide (NO2), normalized difference vegetation index (NDVI), and percentage of green spaces estimated at the census tract level. Breast cancer was identified with ICD-10 code C50. We estimated cause-specific hazard ratios (HR) for the relationship between each indi-vidual exposure and pre and postmenopausal breast cancer risk, using linear and non-linear models. Results: Of the 1,054,180 pre and 744,658 postmenopausal women followed for a median of 10 years, 6,126 and 17,858 developed breast cancer, respectively. Among premenopausal women, only very high levels of PM10 (& GE;46 mu g/m3) were associated with increased cancer risk (compared to lower levels) in non-linear models. Among postmenopausal women, an interquartile range increase in PM2.5 (HR:1.03; 95%CI:1.01-1.04), PM10 (1.03; 1.01-1.05), and NO2 (1.05; 1.02-1.08) were associated with higher cancer risk. NDVI was negatively associated with decreased cancer risk only among postmenopausal women who did not change residence during follow-up (0.84; 0.71-0.99) or who were followed for at least three years (0.82; 0.69-0.98). Discussion: Living in areas with high concentrations of PM2.5, PM10, and NO2 increases breast cancer risk in postmenopausal women while long-term exposure to green spaces may decrease this risk. Only very high con-centrations of PM10 increase breast cancer risk in premenopausal women.

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV1 at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (-0.02 (-0.04, 0)) and FEV1 z-scores (-0.02 (-0.04,-0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV1 at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children’s lower FVC and FEV1, especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure.

Evidence on the impact of the COVID-19 vaccine roll-out on socioeconomic COVID-19-related inequalities is scarce. We analyzed associations between socio-economic deprivation index (SDI) and COVID-19 vac-cination, infection, and hospitalization before and after vaccine rollout in Catalonia, Spain. We conducted a population-based cohort study during September 2020- June 2021 that comprised 2,297,146 adults >40 years of age. We estimated odds ratio of nonvaccination and hazard ratios (HRs) of infection and hospitalization by SDI quintile relative to the least deprived quintile, Q1. Six months after rollout, vaccination coverage differed by SDI quintile in working-age (40-64 years) persons: 81% for Q1, 71% for Q5. Before rollout, we found a pattern of in-creased HR of infection and hospitalization with depriva-tion among working-age and retirement-age (>65 years) persons. After rollout, infection inequalities decreased in both age groups, whereas hospitalization inequalities decreased among retirement-age persons. Our findings suggest that mass vaccination reduced socioeconomic COVID-19-related inequalities.

OBJECTIVE To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines.DESIGN International network cohort study.SETTING Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US.PARTICIPANTS Adults (age a18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021.MAIN OUTCOME MEASURES Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses.RESULTS Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2.CONCLUSIONS In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

Objective We introduce and review the concept of a study-a-thon as a catalyst for open science in medicine, utilizing harmonized real world, observation health data, tools, skills, and methods to conduct network studies, generating insights for those wishing to use study-a-thons for future research. Materials and Methods A series of historical study-a-thons since 2017 to present were reviewed for thematic insights as to the opportunity to accelerate the research method to conduct studies across therapeutic areas. Review of publications and experience of the authors generated insights to illustrate the conduct of study-a-thons, key learning, and direction for those wishing to conduct future such study-a-thons. Results A review of six study-a-thons have provided insights into their scientific impact, and 13 areas of insights for those wishing to conduct future study-a-thons. Defining aspects of the study-a-thon method for rapid, collaborative research through network studies reinforce the need to clear scientific rationale, tools, skills, and methods being collaboratively to conduct a focused study. Well-characterized preparatory, execution and postevent phases, coalescing skills, experience, data, clinical input (ensuring representative clinical context to the research query), and well-defined, logical steps in conducting research via the study-a-thon method are critical. Conclusions A study-a-thon is a focused multiday research event generating reliable evidence on a specific medical topic across different countries and health systems. In a study-a-thon, a multidisciplinary team collaborate to create an accelerated contribution to scientific evidence and clinical practice. It critically accelerates the research process, without inhibiting the quality of the research output and evidence generation, through a reproducible process.
Lay Summary The research process is generally time-consuming, requiring considerable efforts and resources and planning over an extended duration of time before its results, such as via publications. Meanwhile, patients, clinicians, and healthcare providers need evidence to support decision-making from individual treatment to populations and public health policy, and more quickly than we have been used to, to date. This article describes an approach to accelerating the research process, bringing together relevant research and clinical practitioners, whilst not undermining confidence in the research results. Within this article the research event, or study-a-thon, is described, using six examples since 2017, within an international research network, Observational Health Data Sciences and Informatics (OHDSI). These examples help illustrate the steps required to conduct a study-a-thon, the use of health data under the right conditions, and learning from this process for others to consider using study-a-thons to accelerate their own research process where relevant. For the authors and colleagues in the OHDSI network, the open nature of conducting research via study-a-thons can also ensure full transparency of the process for all involved, as well as being able to reproduce results more readily, a key principle in good scientific conduct.