Consol Serra’s research while affiliated with Pompeu Fabra University and other places

Background: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. Objective: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Design, setting, and participants: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. Outcome measurements and statistical analyses: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. Results and limitations: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. Conclusions: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. Patient summary: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.

Background: By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants. Objectives: In this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes. Methods: We analyzed data from two large case-control studies-the New England Bladder Cancer Study (n/n=989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study (n/n=706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis. Results: Of the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte-specific protein 1 (LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in meta-analysis. In the highest exposure category, we observed OR=1.66 (95% CI: 1.17, 2.34, p-trend=0.005) for those with the rs907611-GG genotype and p-interaction=0.02. No other genetic variants tested showed consistent evidence of interaction. Discussion: We found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895.

Background: Multisite musculoskeletal pain is common and disabling. This study aimed to prospectively investigate distribution of musculoskeletal pain anatomically, and explore risk factors for increases/reductions in the number of painful sites. Methods: Using data from participants working in 45 occupational groups in 18 countries, we explored changes in reporting pain at 10 anatomical sites on two occasions 14 months apart. We used descriptive statistics to explore consistency over time in the number of painful sites, and their anatomical distribution. Baseline risk factors for increases/reductions by ≥3 painful sites were explored by random intercept logistic regression that adjusted for baseline number of painful sites. Results: Amongst 8,927 workers, only 20% reported no pain at either time point, and 16% reported ≥3 painful sites both times. After 14 months, the anatomical distribution of pain often changed but there was only an average increase of 0.17 painful sites. Some 14% workers reported a change in painful sites by ≥ 3. Risk factors for an increase of ≥ 3 painful sites included female sex, lower educational attainment, having a physically demanding job, and adverse beliefs about the work-relatedness of musculoskeletal pain. Also predictive were: older age, somatising tendency, and poorer mental health (each of which was also associated with lower odds of reductions of ≥ 3 painful sites). Conclusions: Longitudinally, the number of reported painful sites was relatively stable but the anatomical distribution varied considerably. These findings suggest an important role for central pain sensitisation mechanisms, rather than localised risk factors, among working adults.

Objectives: To assess the association between sickness absence (SA) trajectories by medical diagnoses and exposure to occupational risk factors during pregnancy. Methods: SA trajectories were identified in a cohort of 367 pregnant workers from a healthcare institution (period 2010-2014), based on most frequent diagnosis using sequence analysis. Trajectory 1 included SA episodes due mainly to musculoskeletal disorders (58.86%), trajectory 2 included SA episodes due to pregnancy-related disorders (25.07%) and trajectory 3 included absences mainly covered by pregnancy-related occupational risk benefits (POR) and few SA episodes (16.08%). Exposure to occupational risk factors was assessed by experts and their association with trajectories was analysed using logistic regression. Relative risks (RR) and their 95% confidence intervals (95%CI) were adjusted for age, type of contract and work shift. Results: Trajectory 1 was negatively associated with exposure to safety and ergonomic risks (RR=0.56, 95%CI=0.35-0.90; RR=0.50, 95%CI=0.33-0.77, respectively) and with the highest global risk index (RR=0.68, 95%CI=0.49-0.96). Trajectory 3 was associated with safety and ergonomic risks (RR=2.75, 95%CI=1.59-4.75; RR=3.64, 95%CI=2.18-6.06, respectively) and with the highest global risk index (RR=2.69, 95%CI=1.43-5.01). Nursing aides and nurses had a higher probability of belonging to trajectory 3 (RR 5.58, 95%CI=2.09-14.95 and RR 5.00, 95%CI 2.18-6.06, respectively). Conclusions: Pregnancy-related and musculoskeletal disorders are the most frequent sickness absence diagnosis during pregnancy. Low levels of occupational risk factors exposure were related to absences from work covered mainly by sickness absence. Current social benefits seem to be used as a complementary way to balance work and health during pregnancy.

Healthcare workers have been and still are at the forefront of COVID-19 patient care. Their infection had direct implications and caused important challenges for healthcare performance. The aim of this study is to assess the impact of non-pharmacological preventive measures against COVID-19 among healthcare workers. This study is based on a dynamic cohort of healthcare workers (n = 5543) who had been hired by a Spanish hospital for at least one week during 2020. Negative binomial regression models were used to estimate the incidence rate and the rate ratio (RR) between the two waves (defined from 15 March to 21 June and from 22 June to 31 December), considering natural immunity during the first wave and contextual variables. All models were stratified by socio-occupational variables. The average COVID-19 incidence rate per 1000 worker-days showed a significant reduction between the two waves, dropping from 0.82 (CI95%: 0.73–0.91) to 0.39 (0.35–0.44). The adjusted RR was 0.54 (0.48–0.87) when natural immunity was acquired during the first wave, and contextual variables were considered. The significant reduction of the COVID-19 incidence rate could be explained mainly by improvement in the non-pharmacological preventive interventions. It is needed to identify which measures were more effective. Young workers and those with a replacement contract were identified as vulnerable groups that need greater preventive efforts. Future preparedness plans would benefit from these results.

Background: Case management interventions have shown to be effective to prevent musculoskeletal pain and disability, but a single definition has not been achieved, nor an agreed profile for case managers. Objective: To describe the elements that define case management and case managers tasks for return-to-work of workers with musculoskeletal disorders (MSDs). Methods: A comprehensive computerized search of articles published in English until February 16, 2021 was carried out in several bibliographic databases. Grey literature was obtained through a search of 13 key websites. A peer-review screening of titles and abstracts was carried out. Full text in-depth analysis of the selected articles was performed for data extraction and synthesis of results. Results: We identified 2,422 documents. After full-text screening 31 documents were included for analysis. These were mostly European and North American and had an experimental design. Fifteen documents were published between 2010 to 2021 and of these 7 studies were published from 2015. Fifteen elements were identified being the commonest "return-to-work programme" (44.4%) and "multidisciplinary assessment/interdisciplinary intervention" (44.4%). Of 18 tasks found, the most frequent was "establishing goals and planning return-to-work rehabilitation" (57.7%). Eighteen referral services were identified. Conclusions: Despite there were several elements frequently reported, some elements with scientific evidence of their importance to deal with MSDs (e.g. early return-to-work) were almost not mentioned. This study proposes key points for the description of case management and case managers tasks.

Background INTEVAL_Spain was a complex workplace intervention to prevent and manage musculoskeletal pain among nursing staff. Process evaluations can be especially useful for complex and multifaceted interventions through identifying the success or failure factors of an intervention to improve the intervention implementation. Objectives This study performed a process evaluation of INTEVAL_Spain and aimed to examine whether the intervention was conducted according to the protocol, to investigate the fulfilment of expectations and the satisfaction of workers. Methods The intervention was a two-armed cluster randomized controlled trial and lasted 1 year. The process evaluation included quantitative and qualitative methods. Quantitative methods were used to address the indicators of Steckler and Linnan’s framework. Data on recruitment was collected through a baseline questionnaire for the intervention and the control group. Reach and dose received were collected through participation sheets, dose delivered and fidelity through internal registries, and fulfilment of expectations and satisfaction were collected with two questions at 12-months follow-up. Qualitative methods were used for a content analysis of discussion groups at the end of the intervention led by an external moderator to explore satisfaction and recommendations. The general communication and activities were discussed, and final recommendations were agreed on. Data were synthesized and results were reported thematically. Results The study was performed in two Spanish hospitals during 2016-2017 and 257 workers participated. Recruitment was 62 and 51% for the intervention and the control group, respectively. The reach of the activities ranged from 96% for participatory ergonomics to 5% for healthy diet. The number of sessions offered ranged from 60 sessions for Nordic walking to one session for healthy diet. Fidelity of workers ranged from 100% for healthy diet and 79% for participatory ergonomics, to 42 and 39% for Nordic walking and case management, respectively. Lowest fidelity of providers was 75% for case management and 82% for Nordic walking. Fulfilment of expectations and satisfaction ranged from 6.6/10 and 7.6/10, respectively, for case management to 10/10 together for the healthy diet session. Discussion groups revealed several limitations for most of the activities, mainly focused on a lack of communication between the Champion (coordinator) and the workers. Conclusions This process evaluation showed that the implementation of INTEVAL_Spain was predominantly carried out as intended. Process indicators differed depending on the activity. Several recommendations to improve the intervention implementation process are proposed. Trial registration ISRCTN15780649.

Objective: To describe the characteristics of COVID-19-related episodes in healthcare workers (HCW) of two hospitals. Methods: Prospective study of HCW with COVID-like symptoms and/or who were close contacts of confirmed COVID-19. The percentage of positive PCRs among those with symptoms was calculated, and symptom's positive predictive value and negative predictive value. The characteristics of contacts were described, as well as the secondary clinical attack rate. Results: We registered 1222 episodes of HCW with COVID-like symptoms; 340 (27.8%) had a positive PCR. In 885 episodes, a HCW was a close contact of a confirmed case. In 45.5% of these, the HCW had contact with another HCW. The secondary clinical attack rate of contacts of HCW was 14.5%. Conclusion: We found a high prevalence of disease and transmission between HCW during the first wave of the SARS-CoV-2 pandemic.