Metabolic syndrome and risk of cancer : A study protocol of case-control study using data from the Information System for the Development of Research in Primary Care (SIDIAP) in Catalonia

Funding The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2017 call under the Health Strategy Action 2013-2016 of the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2013-2016 (reference PI17/00914), cofunded with European Union ERDF funds (European Regional Development Fund). TD-S is funded by the Department of Health of the Generalitat de Catalunya, awarded on the 2016 call under the Strategic Plan for Research and Innovation in Health (PERIS) 2016-2020, modality incorporation of scientists and technologists, with reference SLT002/16/00308.Background Metabolic syndrome (MS) is defined by the clustering of specific metabolic disorders in one subject. MS is highly prevalent globally and currently considered a growing public health concern. MS comprises obesity, hypertension, dyslipidaemia and insulin resistance. Mechanisms linking MS with cancer are poorly understood, and it is as yet unknown if MS confers a greater risk than the risk entailed by each of its separate components. The main objective of this study is to compare the association between MS and 14 site-specific cancer against the association between one or two individual components of MS and cancer. The secondary objective is to evaluate the time elapsed since the diagnosis of MS and the subsequent onset of cancer within the 2006-2017 period by sex. Methods and analysis A case-control study will be conducted for the main objective and a cohort of patients with MS will be followed for the evaluation of the second objective. Incident cases of fourteen types of cancer in patients ≥40 years of age diagnosed prospectively will be selected from electronic primary care records in the Information System for Research in Primary Care (SIDIAP database; www.sidiap.org). The SIDIAP database includes anonymous data from 6 million people (80% of the Catalan population) registered in 286 primary healthcare centres. Each matched control (four controls for each case) will have the same inclusion date, the same sex and age (±1 year) than the paired case. Logistic regression and a descriptive analysis and Kaplan-Meier analysis will be performed, in accordance with the objectives. Ethics and dissemination The protocol of the study was approved by the IDIAP Jordi Gol Clinical Research Ethics Committee (protocol P17/212). The study's findings will be published in a peer-reviewed journal and disseminated at national and international conferences and oral presentations to researchers, clinicians and policy makers

Body mass index and waist circumference in relation to the risk of 26 types of cancer : a prospective cohort study of 3.5 million adults in Spain

A high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC. Prospective cohort study with population-based electronic health records from Catalonia, Spain. We included 3,658,417 adults aged ≥ 18 years and free of cancer at baseline between 2006 and 2017. Our main outcome measures were cause-specific hazard ratios (HRs) with 99% confidence intervals (CIs) for incident cancer at 26 anatomical sites. After a median follow-up time of 8.3 years, 202,837 participants were diagnosed with cancer. A higher BMI was positively associated with risk of nine cancers (corpus uteri, kidney, gallbladder, thyroid, colorectal, breast post-menopausal, multiple myeloma, leukemia, non-Hodgkin lymphoma) and was positively associated with three additional cancers among never smokers (head and neck, brain and central nervous system, Hodgkin lymphoma). The respective HRs (per 5 kg/m 2 increment) ranged from 1.04 (99%CI 1.01 to 1.08) for non-Hodgkin lymphoma to 1.49 (1.45 to 1.53) for corpus uteri cancer. While BMI was negatively associated to five cancer types in the linear analyses of the overall population, accounting for non-linearity revealed that BMI was associated to prostate cancer in a U-shaped manner and to head and neck, esophagus, larynx, and trachea, bronchus and lung cancers in an L-shaped fashion, suggesting that low BMIs are an approximation of heavy smoking. Of the 291,305 participants with a WC measurement, 27,837 were diagnosed with cancer. The 99%CIs of the BMI and WC point estimates (per 1 standard deviation increment) overlapped for all cancers. In this large Southern European study, a higher BMI was associated with increased risk of twelve cancers, including four hematological and head and neck (only among never smokers) cancers. Furthermore, BMI and WC showed comparable estimates of cancer risk associated with adiposity. Supplementary information accompanies this paper at 10.1186/s12916-020-01877-3

Association between metabolic syndrome and 13 types of cancer in Catalonia : A matched case-control study

Metabolic syndrome (MS) is the simultaneous occurrence of a cluster of predefined cardiovascular risk factors. Although individual MS components are associated with increased risk of cancer, it is still unclear whether the association between MS and cancer differs from the association between individual MS components and cancer. The aim of this matched case-control study was to estimate the association of 13 types of cancer with (1) MS and (2) the diagnosis of 0, 1 or 2 individual MS components. Cases included 183,248 patients ≥40 years from the SIDIAP database with incident cancer diagnosed between January 2008-December 2017. Each case was matched to four controls by inclusion date, sex and age. Adjusted conditional logistic regression models were used to evaluate the association between MS and cancer risk, comparing the effect of global MS versus having one or two individual components of MS. MS was associated with an increased risk of the following cancers: colorectal (OR: 1.28, 95%CI: 1.23-1.32), liver (OR: 1.93, 95%CI: 1.74-2.14), pancreas (OR: 1.79, 95%CI: 1.63-1.98), post-menopausal breast (OR: 1.10, 95%CI: 1.06-1.15), pre-menopausal endometrial (OR: 2.14, 95%CI: 1.74-2.65), post-menopausal endometrial (OR: 2.46, 95%CI: 2.20-2.74), bladder (OR: 1.41, 95%CI: 1.34-1.48), kidney (OR: 1.84, 95%CI: 1.69-2.00), non-Hodgkin lymphoma (OR: 1.23, 95%CI: 1.10-1.38), leukaemia (OR: 1.42, 95%CI: 1.31-1.54), lung (OR: 1.11, 95%CI: 1.05-1.16) and thyroid (OR: 1.71, 95%CI: 1.50-1.95). Except for prostate, pre-menopause breast cancer and Hodgkin and non-Hodgkin lymphoma, MS is associated with a higher risk of cancer than 1 or 2 individual MS components. Estimates were significantly higher in men than in women for colorectal and lung cancer, and in smokers than in non-smokers for lung cancer. MS is associated with a higher risk of developing 11 types of common cancer, with a positive correlation between number of MS components and risk of cancer

Drug Utilisation Patterns of Alternatives to Ranitidine-Containing Medicines in Patients Treated with Ranitidine:A Network Analysis of Data from Six European National Databases

Introduction: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. Objectives: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. Methods: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). Results: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18–74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017–August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3–3.8/1000 PY was observed in the referral period (September 2019–March 2020), eventually dropping to 0.0–0.4/1000 PY in the post-referral period (April 2020–March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. Conclusions:Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.</p

Residential Proximity to Urban Play Spaces and Childhood Overweight and Obesity in Barcelona, Spain: A Population-Based Longitudinal Study

Altres ajuts: La Marató de TV3, 201621-30Findings on the relationship between play spaces and childhood overweight and obesity are mixed and scarce. This study aimed to investigate the associations between residential proximity to play spaces and the risk of childhood overweight or obesity and potential effect modifiers. This longitudinal study included children living in the city of Barcelona identified in an electronic primary healthcare record database between 2011 and 2018 (N = 75,608). Overweight and obesity were defined according to the WHO standards and we used 300 m network buffers to assess residential proximity to play spaces. We calculated the risk of developing overweight or obesity using Cox proportional hazard models. A share of 29.4% of the study population developed overweight or obesity, but we did not find consistent associations between play space indicators and overweight or obesity. We did not find any consistent sign of effect modification by sex, and only some indications of the modifying role of area socioeconomic status and level of exposure. Although it is not possible to draw clear conclusions from our study, we call for cities to continue increasing and improving urban play spaces with an equitable, healthy, and child-friendly perspectiv

Impact of the COVID-19 pandemic on diagnoses of common mental health disorders in adults in Catalonia, Spain : a population-based cohort study

To investigate how trends in incidence of anxiety and depressive disorders have been affected by the COVID-19 pandemic. Population-based cohort study. Retrospective cohort study from 2018 to 2021 using the Information System for Research in Primary Care (SIDIAP) database in Catalonia, Spain. 3 640 204 individuals aged 18 or older in SIDIAP on 1 March 2018 with no history of anxiety and depressive disorders. The incidence of anxiety and depressive disorders during the prelockdown period (March 2018-February 2020), lockdown period (March-June 2020) and postlockdown period (July 2020-March 2021) was calculated. Forecasted rates over the COVID-19 periods were estimated using negative binomial regression models based on prelockdown data. The percentage of reduction was estimated by comparing forecasted versus observed events, overall and by sex, age and socioeconomic status. The incidence rates per 100 000 person-months of anxiety and depressive disorders were 151.1 (95% CI 150.3 to 152.0) and 32.3 (31.9 to 32.6), respectively, during the prelockdown period. We observed an increase of 37.1% (95% prediction interval 25.5 to 50.2) in incident anxiety diagnoses compared with the expected in March 2020, followed by a reduction of 15.8% (7.3 to 23.5) during the postlockdown period. A reduction in incident depressive disorders occurred during the lockdown and postlockdown periods (45.6% (39.2 to 51.0) and 22.0% (12.6 to 30.1), respectively). Reductions were higher among women during the lockdown period, adults aged 18-34 years and individuals living in the most deprived areas. The COVID-19 pandemic in Catalonia was associated with an initial increase in anxiety disorders diagnosed in primary care but a reduction in cases as the pandemic continued. Diagnoses of depressive disorders were lower than expected throughout the pandemic

Changes in air pollution exposure after residential relocation and body mass index in children and adolescents:A natural experiment study

Air pollution exposure may affect child weight gain, but observational studies provide inconsistent evidence. Residential relocation can be leveraged as a natural experiment by studying changes in health outcomes after a sudden change in exposure within an individual. We aimed to evaluate whether changes in air pollution exposure due to residential relocation are associated with changes in body mass index (BMI) in children and adolescents in a natural experiment study. This population-based study included children and adolescents, between 2 and 17 years, who moved during 2011–2018 and were registered in the primary healthcare in Catalonia, Spain (N = 46,644). Outdoor air pollutants (nitrogen dioxides (NO2), particulate matter &lt;10 μm (PM10) and &lt;2.5 μm (PM2.5)) were estimated at residential census tract level before and after relocation; tertile cut-offs were used to define changes in exposure. Routinely measured weight and height were used to calculate age-sex-specific BMI z-scores. A minimum of 180 days after moving was considered to observe zBMI changes according to changes in exposure using linear fixed effects regression. The majority of participants (60–67% depending on the pollutant) moved to areas with similar levels of air pollution, 15–49% to less polluted, and 14–31% to more polluted areas. Moving to areas with more air pollution was associated with zBMI increases for all air pollutants (β NO2 = 0.10(95%CI 0.09; 0.12), β PM2.5 0.06(0.04; 0.07), β PM10 0.08(0.06; 0.10)). Moving to similar air pollution areas was associated with decreases in zBMI for all pollutants. No associations were found for those moving to less polluted areas. Associations with moving to more polluted areas were stronger in preschool- and primary school-ages. Associations did not differ by area deprivation strata. This large, natural experiment study suggests that increases in outdoor air pollution may be associated with child weight gain, supporting ongoing efforts to lower air pollution levels.</p

Impact of a single-age cohort human papillomavirus vaccination strategy in Catalonia, Spain: Population-based analysis of anogenital warts in men and women

Extensive multiple-age cohort human papillomavirus (HPV) vaccination has proved to be highly effective. We aimed to determine the 8-year population impact of a female single-age cohort HPV vaccination programme on the incidence of anogenital warts (AGW). In 2008, Catalonia initiated a school-based quadrivalent HPV vaccination programme targeting 11-year-old girls, achieving coverage over 80%. Data on diagnoses of AGW and genital herpes were obtained from a population-based database of electronic health records covering 74% of the population. The annual incidence rates from 2009 to 2016 were calculated, stratified by age and sex using Joinpoint regression to estimate trends and annual percentage changes (APC). Among women aged 16-19 years, the AGW incidence decreased by 61% from 2012 to 2016 (APC -19.4%; 95% CI: -30.0 to -7.3). In contrast, the incidence of genital herpes in same-aged women increased throughout the study period (APC 11.1%; 95% CI: 7.2-15.2). Among men aged 20-22 years, the increasing incidence of AGW shifted to a downward trend in 2013 (APC 2009-2013: 17.0%; 95% CI: 8.2-26.5; and APC 2013-2016: -4.5%; 95% CI: -14.6 to 6.9). A similar pattern was observed among men aged 23-25 years (APC 2009-2014: 16.0%; 95% CI: 12.0-20.2; and APC 2014-2016: -6.0%; 95% CI: -18.4 to 8.3). In contrast to AGW, among men aged 20-25 years, the incidence of genital herpes increased over this period. Our study strongly suggests that a single-cohort HPV vaccination strategy with high vaccine uptake not only provides direct benefit in the vaccinated cohor

The natural history of symptomatic COVID-19 during the first wave in Catalonia

The natural history of coronavirus disease 2019 (COVID-19) has yet to be fully described. Here, we use patient-level data from the Information System for Research in Primary Care (SIDIAP) to summarise COVID-19 outcomes in Catalonia, Spain. We included 5,586,521 individuals from the general population. Of these, 102,002 had an outpatient diagnosis of COVID-19, 16,901 were hospitalised with COVID-19, and 5273 died after either being diagnosed or hospitalised with COVID-19 between 1st March and 6th May 2020. Older age, being male, and having comorbidities were all generally associated with worse outcomes. These findings demonstrate the continued need to protect those at high risk of poor outcomes, particularly older people, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death were lower for younger populations, there is a need to limit their role in community transmission

IncidencePrevalence:An R package to calculate population-level incidence rates and prevalence using the OMOP common data model

Purpose: Real-world data (RWD) offers a valuable resource for generating population-level disease epidemiology metrics. We aimed to develop a well-tested and user-friendly R package to compute incidence rates and prevalence in data mapped to the observational medical outcomes partnership (OMOP) common data model (CDM). Materials and Methods: We created IncidencePrevalence, an R package to support the analysis of population-level incidence rates and point- and period-prevalence in OMOP-formatted data. On top of unit testing, we assessed the face validity of the package. To do so, we calculated incidence rates of COVID-19 using RWD from Spain (SIDIAP) and the United Kingdom (CPRD Aurum), and replicated two previously published studies using data from the Netherlands (IPCI) and the United Kingdom (CPRD Gold). We compared the obtained results to those previously published, and measured execution times by running a benchmark analysis across databases. Results: IncidencePrevalence achieved high agreement to previously published data in CPRD Gold and IPCI, and showed good performance across databases. For COVID-19, incidence calculated by the package was similar to public data after the first-wave of the pandemic. Conclusion: For data mapped to the OMOP CDM, the IncidencePrevalence R package can support descriptive epidemiological research. It enables reliable estimation of incidence and prevalence from large real-world data sets. It represents a simple, but extendable, analytical framework to generate estimates in a reproducible and timely manner.</p