E. TAN, D. ROBINSON, A. JOEDICKE, M. MOSSEVELD, K. BODKERGAARD, C. REYES, A. MOAYYERI, A. VOSS, E. MARCONI, F. LAPI, J. REINOLD, K. VERHAMME, L. PEDERSEN, M. BRAITMAIER, M. DE WILDE, M. RUIZ, M. ARAGON, P. BOSCO-LEVY, R. LASSALLE, D. PRIETO-ALHAMBRA and M. SANCHEZ-SANTOS Aten Primaria.2022 Aug; 54(9):102437.doi:10.1007/s00198-023-06837-0 PMID:37436441
We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments.PurposeTo characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns.MethodsWe investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged & GE; 18 years, with & GE; 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022.ResultsOverall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab.ConclusionOur results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.
M. RECALDE, A. PISTILLO, V. DAVILA-BATISTA, M. LEITZMANN, I. ROMIEU, V. VIALLON, H. FREISLING and T. DUARTE-SALLES Aten Primaria.2022 Aug; 54(9):102437.doi:10.1038/s41467-023-39282-y PMID:37391446
Here, the authors show that longer duration and greater degree of overweight and obesity during early adulthood as well as younger age of onset of a high body mass index are associated with a higher risk of 18 cancer types. Single body mass index (BMI) measurements have been associated with increased risk of 13 cancers. Whether life course adiposity-related exposures are more relevant cancer risk factors than baseline BMI (ie, at start of follow-up for disease outcome) remains unclear. We conducted a cohort study from 2009 until 2018 with population-based electronic health records in Catalonia, Spain. We included 2,645,885 individuals aged & GE;40 years and free of cancer in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This study shows that longer duration, greater degree, and younger age of onset of overweight and obesity during early adulthood are positively associated with risk of 18 cancers, including leukemia, non-Hodgkin lymphoma, and among never-smokers, head and neck, and bladder cancers which are not yet considered as obesity-related cancers in the literature. Our findings support public health strategies for cancer prevention focussing on preventing and reducing early overweight and obesity.
Ranzani O, Alari A, Olmos S, Milà C, Rico A, Ballester J, Basagaña X, Chaccour C, Dadvand P, Duarte-Salles T, Foraster M, Nieuwenhuijsen M, Sunyer J, Valentín A, Kogevinas M, Lazcano U, Avellaneda-Gómez C, Vivanco R and Tonne C Aten Primaria.2022 Aug; 54(9):102437.doi:10.1038/s41467-023-38469-7 PMID:37225741
The association between long-term exposure to ambient air pollutants and severe COVID-19 is uncertain. We followed 4,660,502 adults from the general population in 2020 in Catalonia, Spain. Cox proportional models were fit to evaluate the association between annual averages of PM(2.5), NO(2), BC, and O(3) at each participant’s residential address and severe COVID-19. Higher exposure to PM(2.5,) NO(2,) and BC was associated with an increased risk of COVID-19 hospitalization, ICU admission, death, and hospital length of stay. An increase of 3.2 µg/m(3) of PM(2.5) was associated with a 19% (95% CI, 16-21) increase in hospitalizations. An increase of 16.1 µg/m(3) of NO(2) was associated with a 42% (95% CI, 30-55) increase in ICU admissions. An increase of 0.7 µg/m(3) of BC was associated with a 6% (95% CI, 0-13) increase in deaths. O(3) was positively associated with severe outcomes when adjusted by NO(2). Our study contributes robust evidence that long-term exposure to air pollutants is associated with severe COVID-19.
Bennett M, Pistillo A, Recalde M, Reyes C, Freisling H and Duarte-Salles T Aten Primaria.2022 Aug; 54(9):102437.doi:10.1136/bmjopen-2022-066404 PMID:37225269
OBJECTIVE: We aimed to estimate how longitudinal trends in cardiovascular disease, hypertension and type 2 diabetes mellitus incidence in Catalonia, Spain from 2009 to 2018 may differ by age, sex and socioeconomic deprivation. DESIGN: Cohort study using prospectively collected data. SETTING: Electronic health records from primary healthcare centres in Catalonia, Spain. PARTICIPANTS: 3 247 244 adults (=40 years). OUTCOME MEASURES: We calculated the annual incidence (per 1000 persons-year) and incidence rate ratios (IRR) between three time periods of cardiovascular disease, hypertension and type 2 diabetes mellitus to measure trends and changes in incidence during the study period. RESULTS: In 2016-2018 compared with 2009-2012, cardiovascular disease incidence increased in the 40-54 (eg, IRR=1.61, 95% CI: 1.52 to 1.69 in women) and 55-69 age groups. There was no change in cardiovascular disease incidence in women aged 70+ years, and a slight decrease in men aged 70+ years (0.93, 0.90 to 0.95). Hypertension incidence decreased in all age groups for both sexes. Type 2 diabetes mellitus incidence decreased in all age groups for both sexes (eg, 0.72, 0.70 to 0.73 in women aged 55-69 years), except for the 40-54 year age group (eg, 1.09, 1.06 to 1.13 in women). Higher incidence levels were found in the most deprived areas, especially in the 40-54 and 55-69 groups. CONCLUSIONS: Overall cardiovascular disease incidence has increased while hypertension and type 2 diabetes mellitus incidence have decreased in the last years in Catalonia, Spain, with differences in trends by age group and socioeconomic deprivation.
Voss EA, Shoaibi A, Yin Hui Lai L, Blacketer C, Alshammari T, Makadia R, Haynes K, Sena AG, Rao G, van Sandijk S, Fraboulet C, Boyer L, Le Carrour T, Horban S, Morales DR, Martínez Roldán J, Ramírez-Anguita JM, Mayer MA, de Wilde M, John LH, Duarte-Salles T, Roel E, Pistillo A, Kolde R, Maljkovic F, Denaxas S, Papez V, Kahn MG, Natarajan K, Reich C, Secora A, Minty EP, Shah NH, Posada JD, Garcia Morales MT, Bosca D, Cadenas Juanino H, Diaz Holgado A, Pedrera Jiménez M, Serrano Balazote P, García Barrio N, Sen S, Üresin AY, Erdogan B, Belmans L, Byttebier G, Malbrain MLNG, Dedman DJ, Cuccu Z, Vashisht R, Butte AJ, Patel A, Dahm L, Han C, Bu F, Arshad F, Ostropolets A, Nyberg F, Hripcsak G, Suchard MA, Prieto-Alhambra D, Rijnbeek PR, Schuemie MJ and Ryan PB Aten Primaria.2022 Aug; 54(9):102437.doi:10.1016/j.eclinm.2023.101932 PMID:37034358
BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study’s evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell’s palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None.
J. NAVARRO, A. CURRAN, B. RAVENTOS, J. GARCIA, P. SUANZES, V. DESCALZO, P. ALVAREZ, N. ESPINOSA, M. MONTES, I. SUAREZ-GARCIA, C. AMADOR, R. MUGA, V. FALCO and J. BURGOS Aten Primaria.2022 Aug; 54(9):102437.doi:10.1016/j.ejim.2023.01.028 PMID:36764905
Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities in people living with HIV (PLWH). Factors that could lead to a higher prevalence of NAFLD or ease the onset of fibrosis are unclear.Methods: Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively. Factors associated with both were analysed.Results: A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36; these patients had higher risk for significant fibrosis (OR 1.91; 95%CI 1.11-3.28). Factors associated with NAFLD were body mass index (OR 2.05; 95%CI 1.94-2.16) and diabetes (OR 4.68; 95%CI 2.17-10.08), while exposure to integrase strand transfer inhibitors showed a lower risk (OR 0.78; 95%CI 0.62-0.97). In patients with HSI>36, being fe-male (OR 7.33; 95%CI 1.34-40), age (OR 1.22; 95%CI 1.11-1.34), body mass index (OR 1.35; 95%CI 1.18-1.54) and exposure to thymidine analogues (OR 75.4, 95%CI 6.9-823.5) were associated with a higher risk of sig-nificant fibrosis. However, exposure to non-nucleoside reverse transcriptase inhibitors (OR 0.12, 95%CI 0.02-0.89) and time of exposure to protease inhibitors (OR 0.97, 95%CI 0.95-1) showed a lower risk.Conclusion: NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this risk.
Ly NF, Flach C, Lysen TS, Markov E, van Ballegooijen H, Rijnbeek P, Duarte-Salles T, Reyes C, John LH, Karimi L, Reich C, Salek S and Layton D Aten Primaria.2022 Aug; 54(9):102437.doi:10.1007/s40264-023-01286-4 PMID:36976448
INTRODUCTION: Concerns of the persistence and severity of the adverse effects of fluoroquinolones, mainly involving the nervous system, muscles and joints, resulted in the 2018 referral procedure led by the European Medicines Agency (EMA). They advised to stop prescribing fluoroquinolones for infections of mild severity or of a presumed self-limiting course and for prevention of infections, plus to restrict prescriptions in cases of milder infections where other treatment options are available, and restrict in at-risk populations. We aimed to examine whether the impact of EMA regulatory interventions implemented throughout 2018-2019 had an impact on fluoroquinolone prescribing rates. METHODS: A retrospective population-based cohort study was conducted using electronic health care records from six European countries between 2016 and 2021. We analysed monthly incident fluoroquinolone use rates overall and for each fluoroquinolone active substance through flexible modelling via segmented regression to detect time points of trend changes, in monthly percentage change (MPC). RESULTS: The incidence of fluoroquinolone use ranged from 0.7 to 8.0/1000 persons per month over all calendar years. While changes in fluoroquinolone prescriptions were observed over time across countries, these were inconsistent and did not seem to be temporally related to EMA interventions (e.g., Belgium: February/May 2018, MPC – 33.3%, 95% confidence interval [CI] – 35.9 to – 30.7; Germany: February/May 2019, MPC – 12.6%, 95% CI – 13.7 to – 11.6]; UK: January/April 2016, MPC – 4.9%, 95% CI – 6.2 to – 3.6). CONCLUSION: The regulatory action associated with the 2018 referral did not seem to have relevant effects on fluoroquinolone prescribing in primary care.
A. MARKUS, V. STRAUSS, E. BURN, X. LI, A. DELMESTRI, C. REICH, C. YIN, M. MAYER, J. RAMIREZ-ANGUITA, E. MARTI, K. VERHAMME, P. RIJNBEEK, D. PRIETO-ALHAMBRA and A. JODICKE Aten Primaria.2022 Aug; 54(9):102437.doi:10.3389/fphar.2023.1118203 PMID:37033631
Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US.Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards).Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use.Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.
Junior EPP, Normando P, Flores-Ortiz R, Afzal MU, Jamil MA, Bertolin SF, Oliveira VA, Martufi V, de Sousa F, Bashir A, Burn E, Ichihara MY, Barreto ML, Salles TD, Prieto-Alhambra D, Hafeez H and Khalid S Aten Primaria.2022 Aug; 54(9):102437.doi:10.1093/jamia/ocac180 PMID:36264262
OBJECTIVES: The aim of this work is to demonstrate the use of a standardized health informatics framework to generate reliable and reproducible real-world evidence from Latin America and South Asia towards characterizing coronavirus disease 2019 (COVID-19) in the Global South. MATERIALS AND METHODS: Patient-level COVID-19 records collected in a patient self-reported notification system, hospital in-patient and out-patient records, and community diagnostic labs were harmonized to the Observational Medical Outcomes Partnership common data model and analyzed using a federated network analytics framework. Clinical characteristics of individuals tested for, diagnosed with or tested positive for, hospitalized with, admitted to intensive care unit with, or dying with COVID-19 were estimated. RESULTS: Two COVID-19 databases covering 8.3 million people from Pakistan and 2.6 million people from Bahia, Brazil were analyzed. 109 504 (Pakistan) and 921 (Brazil) medical concepts were harmonized to Observational Medical Outcomes Partnership common data model. In total, 341 505 (4.1%) people in the Pakistan dataset and 1 312 832 (49.2%) people in the Brazilian dataset were tested for COVID-19 between January 1, 2020 and April 20, 2022, with a median [IQR] age of 36 [25, 76] and 38 (27, 50); 40.3% and 56.5% were female in Pakistan and Brazil, respectively. 1.2% percent individuals in the Pakistan dataset had Afghan ethnicity. In Brazil, 52.3% had mixed ethnicity. In agreement with international findings, COVID-19 outcomes were more severe in men, elderly, and those with underlying health conditions. CONCLUSIONS: COVID-19 data from 2 large countries in the Global South were harmonized and analyzed using a standardized health informatics framework developed by an international community of health informaticians. This proof-of-concept study demonstrates a potential open science framework for global knowledge mobilization and clinical translation for timely response to healthcare needs in pandemics and beyond.
B. RAVENTOS, A. ABELLAN, A. PISTILLO, C. REYES, E. BURN and T. DUARTE-SALLES Aten Primaria.2022 Aug; 54(9):102437.doi:10.1002/eat.23848 PMID:36352763
Objective To describe the impact of the COVID-19 pandemic on trends in incidence rates (IR) of diagnoses of eating disorders (ED) among adolescents and young adults. Methods Population-based cohort study using primary care records of people aged 10-24 years between January, 2016 and December, 2021 in Catalonia, Spain. IRs were calculated monthly and grouped by the different stages of the COVID-19 pandemic in Catalonia: (1) the pre-lockdown (January, 2016-February, 2020), (2) lockdown (March-June, 2020) and, (3) post-lockdown (July, 2020-December, 2021) periods. Incidence rate ratios (IRR) relative to the corresponding periods in 2018-2019 were calculated. Results A total of 1,179,009 individuals were included. The IR was 9.2 per 100,000 person-months (95% confidence intervals [CI]: 8.9-9.5) during the pre-lockdown period. It decreased during the lockdown period (6.3 per 100,000 person-months [5.5-7.3]), but substantially increased during the following period (19.4. per 100,000 person-months [18.7-20.1]). While large reductions in IRs were observed for both sexes during the lockdown period (IRR 95% CI: 0.65 [0.54-0.78] in females and 0.46 [0.29-0.71] in males), substantial increases during the post-lockdown period were limited to females, and were particularly pronounced among those aged 10-14 and 15-19 years (2.50 [2.23-2.80] and 2.29 [2.07-2.54], respectively). Discussion The COVID-19 pandemic has resulted in a substantial increase in ED diagnoses, primarily driven by higher rates among adolescent females. Public Significance This population-based cohort study demonstrated a substantial increase in incidence rates of eating disorders in primary care following the end of lockdown in Catalonia, Spain, with adolescent girls seen to be most affected.