Publicacions

Transforming the Information System for Research in Primary Care (SIDIAP) in Catalonia to the OMOP Common Data Model and Its Use for COVID-19 Research

B. RAVENTOS, S. FERNANDEZ-BERTOLIN, M. ARAGON, E. VOSS, C. BLACKETER, L. MENDEZ-BOO, M. RECALDE, E. ROEL, A. PISTILLO, C. REYES, S. VAN SANDIJK, L. HALVORSEN, P. RIJNBEEK, E. BURN and T. DUARTE-SALLES
Aten Primaria.2022 Aug; 54(9):102437.doi:10.2147/CLEP.S419481 PMID:37724311

Purpose: The primary aim of this work was to convert the Information System for Research in Primary Care (SIDIAP) from Catalonia, Spain, to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Our second aim was to provide a descriptive analysis of COVID-19-related outcomes among the general population. Patients and Methods: We mapped patient-level data from SIDIAP to the OMOP CDM and we performed more than 3,400 data quality checks to assess its readiness for research. We established a general population cohort as of the 1st March 2020 and identified outpatient COVID-19 diagnoses or tested positive for, hospitalised with, admitted to intensive care units (ICU) with, died with, or vaccinated against COVID-19 up to 30th June 2022.Results: After verifying the high quality of the transformed dataset, we included 5,870,274 individuals in the general population cohort. Of those, 604,472 had either an outpatient COVID-19 diagnosis or positive test result, 58,991 had a hospitalisation, 5,642 had an ICU admission, and 11,233 died with COVID-19. A total of 4,584,515 received a COVID-19 vaccine. People who were hospitalised or died were more commonly older, male, and with more comorbidities. Those admitted to ICU with COVID-19 were generally younger and more often male than those hospitalised and those who died.Conclusion: We successfully transformed SIDIAP to the OMOP CDM. From this dataset, a general population cohort of 5.9 million individuals was identified and their COVID-19-related outcomes over time were described. The transformed SIDIAP database is a valuable resource that can enable distributed network research in COVID-19 and beyond.

Gender-based differences in the meanings and uses of housing for health and everyday life: An intersectional approach

Vásquez-Vera C., Fernández A., Sánchez-Ledesma E., Bennett M. and Borrell C.
Aten Primaria.2022 Aug; 54(9):102437.doi:10.1016/j.wsif.2023.102761 PMID:

It has been shown that there are gender inequalities in the effects of housing on health, which increase when housing conditions worsen. This study explored the different forms of meaning and uses of housing, according to gender and housing situation, as possible mechanisms that operate in the gender differences of health outcomes associated with different housing situations. A qualitative study was conducted through 9 non-mixed discussion groups (women and men) with people with and without housing insecurity. They reflected on the meanings and uses of housing and its link with health. The content analysis identified discourses on the sense of belonging, testimonial housing, daily practices and embodiment of housing experiences, which varied according to gender and residential situation. A complex and intersectional look is needed in the approach to the residential phenomenon, to achieve a greater understanding of the unequal effects on people’s health. © 2023 Elsevier Ltd

Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe

Moreno-Martos D., Verhamme K., Ostropolets A., Kostka K., Duarte-Sales T., Prieto-Alhambra D., Alshammari T.M., Alghoul H., Ahmed W.-U.-R., Blacketer C., DuVall S., Lai L., Matheny M., Nyberg F., Posada J., Rijnbeek P., Spotnitz M., Sena A., Shah N., Suchard M., Chan You S., Hripcsak G., Ryan P. and Morales D.
Aten Primaria.2022 Aug; 54(9):102437.doi:10.12688/wellcomeopenres.17403.3 PMID:

Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a ‘diagnosed’ and ‘hospitalized’ cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes. Copyright: © 2023 Moreno-Martos D et al.

12-year evolution of multimorbidity patterns among older adults based on Hidden Markov Models

A. ROSO-LLORACH, D. VETRANO, C. TREVISAN, S. FERNANDEZ, M. GUISADO-CLAVERO, L. CARRASCO-RIBELLES, L. FRATIGLIONI, C. VIOLAN and A. CALDERON-LARRANAGA
Aten Primaria.2022 Aug; 54(9):102437.doi:10.18632/aging.204395 PMID:36435509

Background: The evolution of multimorbidity patterns during aging is still an under-researched area. We lack evidence concerning the time spent by older adults within one same multimorbidity pattern, and their transitional probability across different patterns when further chronic diseases arise. The aim of this study is to fill this gap by exploring multimorbidity patterns across decades of age in older adults, and longitudinal dynamics among these patterns.Methods: Longitudinal study based on the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) on adults >= 60 years (N=3,363). Hidden Markov Models were applied to model the temporal evolution of both multimorbidity patterns and individuals’ transitions over a 12-year follow-up.Findings: Within the study population (mean age 76.1 years, 66.6% female), 87.2% had >= 2 chronic conditions at baseline. Four longitudinal multimorbidity patterns were identified for each decade. Individuals in all decades showed the shortest permanence time in an Unspecific pattern lacking any overrepresented diseases (range: 4.6-10.9 years), but the pattern with the longest permanence time varied by age. Sexagenarians remained longest in the Psychiatric-endocrine and sensorial pattern (15.4 years); septuagenarians in the Neuro-vascular and skin-sensorial pattern (11.0 years); and octogenarians and beyond in the Neuro-sensorial pattern (8.9 years). Transition probabilities varied across decades, sexagenarians showing the highest levels of stability.Interpretation: Our findings highlight the dynamism and heterogeneity underlying multimorbidity by quantifying the varying permanence times and transition probabilities across patterns in different decades. With increasing age, older adults experience decreasing stability and progressively shorter permanence time within one same multimorbidity pattern.

Flecainide and risk of skin neoplasms: Results of a large nested case-control study in Spain and Denmark

C. REYES, L. LEON-MUNOZ, A. PISTILLO, S. SCHMIDT, K. KRISTENSEN, D. PUENTE, A. LLORENTE-GARCIA, C. HUERTA-ALVAREZ, A. POTTEGARD and T. DUARTE-SALLES
Aten Primaria.2022 Aug; 54(9):102437.doi:10.3389/fphar.2022.1002451 PMID:36618916

Background:A previous study in Denmark suggested an increased melanoma risk associated with the use of flecainide. Objective:To study the association between flecainide use and the risk of melanoma and non-melanoma skin cancer in Spain and Denmark. Methods:We conducted a multi-database case-control study in (database/study period) Spain (SIDIAP/2005-2017 and BIFAP/2007-2017) and Denmark (Danish registries/2001-2018). We included incident cases of melanoma or non-melanoma skin cancer (NMSC) aged >= 18 with >= 2 years of previous data (>= 10 years for Denmark) before the skin cancer and matched them to controls (10:1 by age and sex). We excluded persons with immunosuppression or previous cancer. We defined ever-use as any prescription fill and high-use as a cumulative dose of at least 200 g (reference: never-use). We categorized a cumulative dose for a dose-response assessment. We used conditional logistic regression to compute ORs (95% CI) adjusted for photosensitizing, anti-neoplastic, disease-specific drugs and comorbidities. Results:The total numbers of melanoma/NMSC cases included were 7,809/64,230 in SIDIAP, 4,661/31,063 in BIFAP, and 27,978/152,821 in Denmark. In Denmark, high-use of flecainide was associated with increased adjusted ORs of skin cancer compared with never-use [melanoma: OR 1.97 (1.38-2.81); NMSC: OR 1.34 (1.15-1.56)]. In Spain, an association between high-use of flecainide and NMSC was also observed [BIFAP: OR 1.42 (1.04-1.93); SIDIAP: OR 1.19 (0.95-1.48)]. There was a non-significant dose-response pattern for melanoma in Denmark and no apparent dose-response pattern for NMSC in any of the three databases. We found similar results for ever-use of flecainide. Conclusion:Flecainide use was associated with an increased risk of melanoma (Denmark only) and NMSC (Denmark and Spain) but without substantial evidence of dose-response patterns. Further studies are needed to assess for possible unmeasured confounders.

Data Resource Profile: The Information System for Research in Primary Care (SIDIAP)

M. RECALDE, C. RODRIGUEZ, E. BURN, M. FAR, D. GARCIA, J. CARRERE-MOLINA, M. BENITEZ, A. MOLERAS, A. PISTILLO, B. BOLIBAR, M. ARAGON and T. DUARTE-SALLES
Aten Primaria.2022 Aug; 54(9):102437.doi:10.1093/ije/dyac068 PMID:35415748

Polypharmacy Patterns in Multimorbid Older People with Cardiovascular Disease: Longitudinal Study

N. VILLEN, A. ROSO-LLORACH, C. GALLEGO-MOLL, M. DANES-CASTELLS, S. FERNANDEZ-BERTOLIN, A. TRONCOSO-MARINO, M. MONTEAGUDO, E. AMADO and C. VIOLAN
Aten Primaria.2022 Aug; 54(9):102437.doi:10.3390/geriatrics7060141 PMID:36547277

(1) Introduction: Cardiovascular disease is associated with high mortality, especially in older people. This study aimed to characterize the evolution of combined multimorbidity and polypharmacy patterns in older people with different cardiovascular disease profiles. (2) Material and methods: This longitudinal study drew data from the Information System for Research in Primary Care in people aged 65 to 99 years with profiles of cardiovascular multimorbidity. Combined patterns of multimorbidity and polypharmacy were analysed using fuzzy c-means clustering techniques and hidden Markov models. The prevalence, observed/expected ratio, and exclusivity of chronic diseases and/or groups of these with the corresponding medication were described. (3) Results: The study included 114,516 people, mostly men (59.6%) with a mean age of 78.8 years and a high prevalence of polypharmacy (83.5%). The following patterns were identified: Mental, behavioural, digestive and cerebrovascular; Neuropathy, autoimmune and musculoskeletal; Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological; Non-specific; Multisystemic; Respiratory, cardiovascular, behavioural and genitourinary; Diabetes and ischemic cardiopathy; and Cardiac. The prevalence of overrepresented health problems and drugs remained stable over the years, although by study end, cohort survivors had more polypharmacy and multimorbidity. Most people followed the same pattern over time; the most frequent transitions were from Non-specific to Mental, behavioural, digestive and cerebrovascular and from Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological to Non-specific. (4) Conclusions: Eight combined multimorbidity and polypharmacy patterns, differentiated by sex, remained stable over follow-up. Understanding the behaviour of different diseases and drugs can help design individualised interventions in populations with clinical complexity.

Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in Catalonia, Spain

E. BURN, E. ROEL, A. PISTILLO, S. FERNANDEZ-BERTOLIN, M. ARAGON, B. RAVENTOS, C. REYES, K. VERHAMME, P. RIJNBEEK, X. LI, V. STRAUSS, D. PRIETO-ALHAMBRA and T. DUARTE-SALLES
Aten Primaria.2022 Aug; 54(9):102437.doi:10.1038/s41467-022-34669-9 PMID:36418321

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Here we compare rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 with the background (expected) rates in the general population. In addition, we compare the rates of the same adverse events among persons infected with SARS-CoV-2 with background rates. Primary care and linked hospital data from Catalonia, Spain informed the study, with participants vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-23/06/2021), COVID-19 cases (01/09/2020-23/06/2021) or present in the database as of 01/01/2017. We included 2,021,366 BNT162b2 (1,327,031 with 2 doses), 592,408 ChAdOx1, 174,556 COVID-19 cases, and 4,573,494 background participants. Standardised incidence ratios for venous thromboembolism were 1.18 (95% CI 1.06-1.32) and 0.92 (0.81-1.05) after first- and second dose BNT162b2, and 0.92 (0.71-1.18) after first dose ChAdOx1. The standardised incidence ratio for venous thromboembolism in COVID-19 was 10.19 (9.43-11.02). Standardised incidence ratios for arterial thromboembolism were 1.02 (0.95-1.09) and 1.04 (0.97-1.12) after first- and second dose BNT162b2, 1.06 (0.91-1.23) after first-dose ChAdOx1 and 4.13 (3.83-4.45) for COVID-19. Standardised incidence ratios for thrombocytopenia were 1.49 (1.43-1.54) and 1.40 (1.35-1.45) after first- and second dose BNT162b2, 1.28 (1.19-1.38) after first-dose ChAdOx1 and 4.59 (4.41- 4.77) for COVID-19. While rates of thrombosis with thrombocytopenia were generally similar to background rates, the standardised incidence ratio for pulmonary embolism with thrombocytopenia after first-dose BNT162b2 was 1.70 (1.11-2.61). These findings suggest that the safety profiles of BNT162b2 and ChAdOx1 are similar, with rates of adverse events seen after vaccination typically similar to background rates. Meanwhile, rates of adverse events are much increased for COVID-19 cases further underlining the importance of vaccination.
Population-based studies can provide information on the safety of COVID-19 vaccines. Here the authors report the rates of thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in Catalonia, Spain and compare them with the background (expected) rates in the general population.

Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom

E. BURN, X. LI, A. DELMESTRI, N. JONES, T. DUARTE-SALLES, C. REYES, E. MARTINEZ-HERNANDEZ, E. MARTI, K. VERHAMME, P. RIJNBEEK, V. STRAUSS and D. PRIETO-ALHAMBRA
Aten Primaria.2022 Aug; 54(9):102437.doi:10.1038/s41467-022-34668-w PMID:36418291

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]).
Population-based studies can provide information on the safety of COVID-19 vaccines. Here the authors report the rates thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom and compare them with the background (expected) rates in the general population.

Air pollution and green spaces in relation to breast cancer risk among pre and postmenopausal women: A mega cohort from Catalonia

I. TERRE-TORRAS, M. RECALDE, Y. DIAZ, J. DE BONT, M. BENNETT, M. ARAGON, M. CIRACH, C. O'CALLAGHAN-GORDO, M. NIEUWENHUIJSEN and T. DUARTE-SALLES
Aten Primaria.2022 Aug; 54(9):102437.doi:10.1016/j.envres.2022.113838 PMID:35810806

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.

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