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

Trends of use and characterisation of anti-dementia drugs users:a large multinational-network population-based study

Background: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. Setting: Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model. Methods: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). Results: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. Conclusions: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.</p

Trends of use and characterisation of anti-dementia drugs users:a large multinational-network population-based study

Background: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. Setting: Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model. Methods: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). Results: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. Conclusions: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.</p

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

Effectiveness of COVID-19 vaccines against severe COVID-19 among patients with cancer in Catalonia, Spain

Patients with cancer were excluded from pivotal randomized clinical trials of COVID-19 vaccine products, and available observational evidence on vaccine effectiveness (VE) focused mostly on mild, and not severe COVID-19, which is the ultimate goal of vaccination for high-risk groups. Here, using primary care electronic health records from Catalonia, Spain (SIDIAP), we built two large cohorts of vaccinated and matched control cancer patients with a primary vaccination scheme (n = 184,744) and a booster (n = 108,534). Most patients received a mRNA-based product in primary (76.2%) and booster vaccination (99.9%). Patients had 51.8% (95% CI 40.3%−61.1%) and 58.4% (95% CI 29.3%−75.5%) protection against COVID-19 hospitalization and COVID-19 death respectively after full vaccination (two-doses) and 77.9% (95% CI 69.2%−84.2%) and 80.2% (95% CI 63.0%−89.4%) after booster. Compared to primary vaccination, the booster dose provided higher peak protection during follow-up. Calibration of VE estimates with negative outcomes, and sensitivity analyses with slight different population and COVID-19 outcomes definitions provided similar results. Our results confirm the role of primary and booster COVID-19 vaccination in preventing COVID-19 severe events in patients with cancer and highlight the need for the additional dose in this population.</p

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

The burden of long COVID: a multinational cohort analysis of Spanish and UK data including SARS-CoV-2 infections, reinfections, and matched contemporaneous test negative controls

As limited data was available on the effect of persisting COVID-19 symptoms, we characterised long COVID and identified key symptoms associated with persistent disease. Using primary care data from Spain and UK, we estimated incidence rates of long COVID in the population and among COVID-19 patients over time. Subsequently, we investigated which WHO-listed symptoms were particularly differential for long COVID by comparing their frequency in COVID-19 patients vs matched test-negative controls. Lastly, we compared persistent symptoms after first infections vs. reinfections. Fortunately, the proportion of COVID-19 cases resulting in long COVID declined over the study period. Risk for altered smell/taste, dyspnoea, and fatigue were consistently higher in long COVID patient vs controls [RR between 5.97-1.09]. All persistent symptoms were less common after reinfection than first infection. More research is needed into the definition of long COVID, and the effect of interventions to minimise the risk and impact of persistent symptoms

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