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Objective: Multiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE)., Methods: We conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy., Results: We characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80-88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66-83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults., Conclusion: Treatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines., Competing Interests: Declarations of competing interest DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department. James Brash and Hanne van Ballegooijen are employees of IQVIA. All other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)., Methods: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control., Results: More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment., Conclusion: Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2)., Methods: We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates., Findings: A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44-0·67) in CPRD GOLD, 0·48 (0·34-0·68) in CPRD AURUM, 0·71 (0·55-0·91) in SIDIAP, and 0·59 (0·40-0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60-1·20] in CPRD GOLD and 0·84 [0·74-0·94] in CPRD AURUM)., Interpretation: Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults., Funding: National Institute for Health and Care Research., Competing Interests: Declaration of interests DP-A's department has received grants from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, UCB Biopharma, the European Medicines Agency, and the Innovative Medicines Initiative. DP-A's research group has received consultancy fees from Astra Zeneca and UCB Biopharma. DP-A's department has organised training programmes funded or supported by Amgen, Astellas, Janssen, Synapse Management Partners, and UCB Biopharma. RK's research group has received consultancy fees from AstraZeneca and the Estonian Ministry of Social Affairs through RITA CORIVA and RITA MAITT (Machine learning and AI powered public services) projects. AU reports funding from the European Regional Development Fund (RITA 1/02–120) for her institution (Department of Family Medicine and Public Health, University of Tartu). HMEN reports support from the European Health Data and Evidence Network project grant, Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 806968) for harmonisation of the Norwegian registry data into the Observational Medical Outcomes Partnership (OMOP) common data model (CDM). TD-S reports funding from the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 806968) for the institute to map the SIDIAP data to the OMOP CDM. This initiative received support from the EU Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster., Methods: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards., Results: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15])., Conclusion: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© 2022. The Author(s).)

Evidence on the impact of the COVID-19 vaccine rollout on socioeconomic COVID-19-related inequalities is scarce. We analyzed associations between socioeconomic deprivation index (SDI) and COVID-19 vaccination, infection, and hospitalization before and after vaccine rollout in Catalonia, Spain. We conducted a population-based cohort study during September 2020-June 2021 that comprised 2,297,146 adults >40 years of age. We estimated odds ratio of nonvaccination and hazard ratios (HRs) of infection and hospitalization by SDI quintile relative to the least deprived quintile, Q1. Six months after rollout, vaccination coverage differed by SDI quintile in working-age (40-64 years) persons: 81% for Q1, 71% for Q5. Before rollout, we found a pattern of increased HR of infection and hospitalization with deprivation among working-age and retirement-age (>65 years) persons. After rollout, infection inequalities decreased in both age groups, whereas hospitalization inequalities decreased among retirement-age persons. Our findings suggest that mass vaccination reduced socioeconomic COVID-19-related inequalities.

Purpose: We aim to compare the severity of infections between omicron and delta variants in 609,352 SARS-CoV-2 positive cases using local hospitalization, vaccination, and variants data from the Catalan Health Care System (which covers around 7. 8 million people)., Methods: We performed a substitution model to establish the increase in transmissibility of omicron using variant screening data from primary care practices (PCP) and hospital admissions. In addition, we used this data from PCP to establish the two periods when delta and omicron were, respectively, dominant (above 95% of cases). After that, we performed a population-based cohort analysis to calculate the rates of hospital and intensive care unit (ICU) admissions for both periods and to estimate reduction in severity. Rate ratios (RR) and 95% confidence intervals (95% CI) were calculated and stratified by age and vaccination status. In a second analysis, the differential substitution model in primary care vs. hospitals allowed us to obtain a population-level average change in severity., Results: We have included 48,874 cases during the delta period and 560,658 during the omicron period. During the delta period, on average, 3.8% of the detected cases required hospitalization for COVID-19. This percentage dropped to 0.9% with omicron [RR of 0.46 (95% CI: 0.43 to 0.49)]. For ICU admissions, it dropped from 0.8 to 0.1% [RR 0.25 (95% CI: 0.21 to 0.28)]. The proportion of cases hospitalized or admitted to ICU was lower in the vaccinated groups, independently of the variant. Omicron was associated with a reduction in risk of admission to hospital and ICU in all age and vaccination status strata. The differential substitution models showed an average RR between 0.19 and 0.50., Conclusion: Both independent methods consistently show an important decrease in severity for omicron relative to delta. The systematic reduction happens regardless of age. The severity is also reduced for non-vaccinated and vaccinated groups, but it remains always higher in the non-vaccinated population. This suggests an overall reduction in severity, which could be intrinsic to the omicron variant. The fact is that the RR in ICU admission is systematically smaller than in hospitalization points in the same direction., Competing Interests: EA-L, CP, and SA report a relationship with Janssen-Cilag SA that includes consulting or advisory. DP-A reports a relationship with Amgen Inc that includes consulting or advisory, funding grants, and speaking and lecture fees. DP-A reports a relationship with Chesi-Taylor that includes funding grants. DP-A reports a relationship with Novartis AG that includes funding grants. DP-A reports a relationship with UCB Biopharma that includes consulting or advisory, funding grants, and speaking and lecture fees. DP-A reports a relationship with Astellas Pharma Inc that includes consulting or advisory. DP-A reports a relationship with AstraZeneca that includes consulting or advisory. DP-A reports a relationship with Johnson and Johnson SA that includes consulting or advisory. Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programs organized by co-author DP-A's department and open for external participants. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Català, Coma, Alonso, Andrés, Blanco, Antón, Bordoy, Cardona, Fina, Martró, Medina, Mora, Saludes, Prats, Prieto-Alhambra and Alvarez-Lacalle.)

Objective: To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events., Design: Population based historical rate comparison study and self-controlled case series analysis., Setting: Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data., Participants: 8 330 497 people who received at least one dose of covid-19 vaccines ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, or Ad.26.COV2.S between the rollout of the vaccination campaigns and end of data availability (UK: 9 May 2021; Spain: 30 June 2021). The study sample also comprised a cohort of 735 870 unvaccinated individuals with a first positive reverse transcription polymerase chain reaction test result for SARS-CoV-2 from 1 September 2020, and 14 330 080 participants from the general population., Main Outcome Measures: Outcomes were incidence of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. Incidence rates were estimated in the 21 days after the first vaccine dose, 90 days after a positive test result for SARS-CoV-2, and between 2017 and 2019 for background rates in the general population cohort. Indirectly standardised incidence ratios were estimated. Adjusted incidence rate ratios were estimated from the self-controlled case series., Results: The study included 4 376 535 people who received ChAdOx1 nCoV-19, 3 588 318 who received BNT162b2, 244 913 who received mRNA-1273, and 120 731 who received Ad26.CoV.2; 735 870 people with SARS-CoV-2 infection; and 14 330 080 people from the general population. Overall, post-vaccine rates were consistent with expected (background) rates for Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome. Self-controlled case series was conducted only for Bell's palsy, given limited statistical power, but with no safety signal seen for those vaccinated. Rates were, however, higher than expected after SARS-CoV-2 infection. For example, in the data from the UK, the standardised incidence ratio for Bell's palsy was 1.33 (1.02 to 1.74), for encephalomyelitis was 6.89 (3.82 to 12.44), and for Guillain-Barré syndrome was 3.53 (1.83 to 6.77). Transverse myelitis was rare (<5 events in all vaccinated cohorts) and could not be analysed., Conclusions: No safety signal was observed between covid-19 vaccines and the immune mediated neurological events of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. An increased risk of Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome was, however, observed for people with SARS-CoV-2 infection., Competing Interests: Contributors: XL and BR are joint first authors. DP-A, EB, and TD-S are joint senior authors. XL, BR, DP-A, TD-S, EB, and VS conceived the study and contributed to the study design. XL, BR, ER, and AP conducted the statistical analyses. XL, BR, ER, VS, DP-A, EB, and TD-S interpreted the results and wrote the manuscript. All authors contributed to writing the manuscript, approved the final version, and had final responsibility for the decision to submit for publication. TD-S, EB, and DP-A are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Competing interests: All authors have completed the ICMJE disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare the following interests: DP-A receives funding from the UK National Institute for Health Research (NIHR) in the form of a senior research fellowship and from the Oxford NIHR Biomedical Research Centre. XL receives the Clarendon Fund and Brasenose College scholarship (University of Oxford) to support her DPhil study. DP-A’s research group has received research grants from the European Medicines Agency; the Innovative Medicines Initiative; and Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, AstraZeneca, and UCB Biopharma., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

The relationship between cancer and coronavirus disease 2019 (COVID-19) infection and severity remains poorly understood. We conducted a population-based cohort study between 1 March and 6 May 2020 describing the associations between cancer and risk of COVID-19 diagnosis, hospitalisation and COVID-19-related death. Data were obtained from the Information System for Research in Primary Care (SIDIAP) database, including primary care electronic health records from ~80% of the population in Catalonia, Spain. Cancer was defined as any primary invasive malignancy excluding non-melanoma skin cancer. We estimated adjusted hazard ratios (aHRs) for the risk of COVID-19 (outpatient) clinical diagnosis, hospitalisation (with or without a prior COVID-19 diagnosis) and COVID-19-related death using Cox proportional hazard regressions. Models were estimated for the overall cancer population and by years since cancer diagnosis (<1 year, 1-5 years and ≥5 years), sex, age and cancer type; and adjusted for age, sex, smoking status, deprivation and comorbidities. We included 4 618 377 adults, of which 260 667 (5.6%) had a history of cancer. A total of 98 951 individuals (5.5% with cancer) were diagnosed, and 6355 (16.4% with cancer) were directly hospitalised with COVID-19. Of those diagnosed, 6851 were subsequently hospitalised (10.7% with cancer), and 3227 died without being hospitalised (18.5% with cancer). Among those hospitalised, 1963 (22.5% with cancer) died. Cancer was associated with an increased risk of COVID-19 diagnosis (aHR: 1.08; 95% confidence interval [1.05-1.11]), direct COVID-19 hospitalisation (1.33 [1.24-1.43]) and death following hospitalisation (1.12 [1.01-1.25]). These associations were stronger for patients recently diagnosed with cancer, aged <70 years, and with haematological cancers. These patients should be prioritised in COVID-19 vaccination campaigns and continued non-pharmaceutical interventions., (© 2021 UICC.)

Context: A comprehensive understanding of the association between body mass index (BMI) and coronavirus disease 2019 (COVID-19) is still lacking., Objective: To investigate associations between BMI and risk of COVID-19 diagnosis, hospitalization with COVID-19, and death after a COVID-19 diagnosis or hospitalization (subsequent death), accounting for potential effect modification by age and sex., Design: Population-based cohort study., Setting: Primary care records covering >80% of the Catalan population, linked to regionwide testing, hospital, and mortality records from March to May 2020., Participants: Adults (≥18 years) with at least 1 measurement of weight and height., Main Outcome Measures: Hazard ratios (HR) for each outcome., Results: We included 2 524 926 participants. After 67 days of follow-up, 57 443 individuals were diagnosed with COVID-19, 10 862 were hospitalized with COVID-19, and 2467 had a subsequent death. BMI was positively associated with being diagnosed and hospitalized with COVID-19. Compared to a BMI of 22 kg/m2, the HR (95% CI) of a BMI of 31 kg/m2 was 1.22 (1.19-1.24) for diagnosis and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalization without and with a prior outpatient diagnosis, respectively. The association between BMI and subsequent death was J-shaped, with a modestly higher risk of death among individuals with BMIs ≤ 19 kg/m2 and a more pronounced increasing risk for BMIs ≥ 40 kg/m2. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients., Conclusions: There is a monotonic association between BMI and COVID-19 diagnosis and hospitalization risks but a J-shaped relationship with mortality. More research is needed to unravel the mechanisms underlying these relationships., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity., Methods: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status., Results: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity., Conclusion: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies., (© 2021. The Author(s).)

Objective: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza., Methods: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization., Results: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%)., Conclusion: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza., Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes., Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza ( n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events., Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent., Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies., (©2021 The Authors; Published by the American Association for Cancer Research.)

Objectives: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018., Methods: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death., Results: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable ( n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza., Conclusions: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Monitoring transmission is a prerequisite for containing COVID-19. We report on effective potential growth (EPG) as a novel measure for the early identification of local outbreaks based on primary care electronic medical records (EMR) and PCR-confirmed cases. Secondly, we studied whether increasing EPG precedes local hospital and intensive care (ICU) admissions and mortality. Population-based cohort including all Catalan citizens' PCR tests, hospitalization, intensive care (ICU) and mortality between 1/07/2020 and 13/09/2020; linked EMR covering 88.6% of the Catalan population was obtained. Nursing home residents were excluded. COVID-19 counts were ascertained based on EMR and PCRs separately. Weekly empirical propagation (ρ 7 ) and 14-day cumulative incidence (A 14 ) and 95% confidence intervals were estimated at care management area (CMA) level, and combined as EPG = ρ 7 × A 14 . Overall, 7,607,201 and 6,798,994 people in 43 CMAs were included for PCR and EMR measures, respectively. A14, ρ 7 , and EPG increased in numerous CMAs during summer 2020. EMR identified 2.70-fold more cases than PCRs, with similar trends, a median (interquartile range) 2 (1) days earlier, and better precision. Upticks in EPG preceded increases in local hospital admissions, ICU occupancy, and mortality. Increasing EPG identified localized outbreaks in Catalonia, and preceded local hospital and ICU admissions and subsequent mortality. EMRs provided similar estimates to PCR, but some days earlier and with better precision. EPG is a useful tool for the monitoring of community transmission and for the early identification of COVID-19 local outbreaks., Competing Interests: DP-A department has received consultancy fees from UCB Biopharma. DP-A department has received speaker fees from AMGEN. Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DP-A department and open for external participants. CP has received consultancy fees from Janssen. None of these relationships has directly funded this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Catala, Coma, Alonso, Álvarez-Lacalle, Cordomi, López, Fina, Medina-Peralta, Prats and Prieto-Alhambra.)

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.

Background: Currently, there is a missing link in the natural history of COVID-19, from first (usually milder) symptoms to hospitalization and/or death. To fill in this gap, we characterized COVID-19 patients at the time at which they were diagnosed in outpatient settings and estimated 30-day hospital admission and fatality rates., Methods: This was a population-based cohort study., Data were obtained from Information System for Research in Primary Care (SIDIAP)-a primary-care records database covering >6 million people (>80% of the population of Catalonia), linked to COVID-19 reverse transcriptase polymerase chain reaction (RT-PCR) tests and hospital emergency, inpatient and mortality registers. We included all patients in the database who were ≥15 years old and diagnosed with COVID-19 in outpatient settings between 15 March and 24 April 2020 (10 April for outcome studies). Baseline characteristics included socio-demographics, co-morbidity and previous drug use at the time of diagnosis, and polymerase chain reaction (PCR) testing and results., Study outcomes included 30-day hospitalization for COVID-19 and all-cause fatality., Results: We identified 118 150 and 95 467 COVID-19 patients for characterization and outcome studies, respectively. Most were women (58.7%) and young-to-middle-aged (e.g. 21.1% were 45-54 years old). Of the 44 575 who were tested with PCR, 32 723 (73.4%) tested positive. In the month after diagnosis, 14.8% (14.6-15.0) were hospitalized, with a greater proportion of men and older people, peaking at age 75-84 years. Thirty-day fatality was 3.5% (95% confidence interval: 3.4% to 3.6%), higher in men, increasing with age and highest in those residing in nursing homes [24.5% (23.4% to 25.6%)]., Conclusion: COVID-19 infections were widespread in the community, including all age-sex strata. However, severe forms of the disease clustered in older men and nursing-home residents. Although initially managed in outpatient settings, 15% of cases required hospitalization and 4% died within a month of first symptoms. These data are instrumental for designing deconfinement strategies and will inform healthcare planning and hospital-bed allocation in current and future COVID-19 outbreaks., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Strontium ranelate use, compared with oral bisphosphonates, is not associated with increased risk of AMI in patients with no contraindications for SR use. However, current strontium ranelate (compared with current bisphosphonate) appears associated with 25-30% excess risk of VTE and 35% excess risk of CVDeath., Introduction: Evaluate the risk of cardiac and thromboembolic events among new users of SR and oral BPs without contraindications for SR., Methods: We conducted three multi-national, multi-database (Aarhus-Denmark, HSD-Italy, IPCI-Netherlands, SIDIAP-Spain, THIN-UK) case-control studies nested within a cohort of new users of SR/BP. We matched cases of acute myocardial infarction (AMI), venous thromboembolism (VTE), and cardiovascular death (CVDeath), up to 10 controls on gender, year of birth, index date, and country. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) according to current SR vs current BP use and current vs past SR use, adjusting for potential confounders. Data were pooled using random effects meta-analysis., Results: No excess risk of AMI (5477 cases/54,674 controls) was found with current SR vs current BP (OR 0.89 (95%CI 0.70, 1.12)) nor with current vs past SR use (0.71(0.56, 0.91)). For VTE (5614 cases/6036 controls), an excess risk was found with current SR compared with current BP use, 1.24 (0.96, 1.61), and current vs past SR use, 1.30 (1.04, 1.62). For CVDeath (3019 cases/29,871 controls), an increased risk was seen with current SR vs current BP use, 1.35 (1.02, 1.80), but not with current vs past SR use (0.68 (0.48, 0.96))., Conclusion: In patients without contraindications for SR, we found no evidence of an increased risk of AMI but a 25-30% excess risk of VTE and a 35% excess risk of CVDeath with current SR vs current BP users. This is despite a reduction in risk in CVDeath with current vs past SR users. The latter disparity could still be partially explained by cessation of preventative therapies in end-of-life or residual confounding by indication.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

This paper demonstrates a large post-fracture anti-osteoporosis treatment gap in the period 2005 to 2015. The gap was stable in Denmark at around 88-90%, increased in Catalonia from 80 to 88%, and started to increase in the UK towards the end of our study. Improved post-fracture care is needed., Introduction: Patients experiencing a fragility fracture are at high risk of subsequent fractures, particularly within the first 2 years after the fracture. Previous studies have demonstrated that only a small proportion of fracture patients initiate therapy with an anti-osteoporotic medication (AOM), despite the proven fracture risk reduction of such therapies. The aim of this paper is to evaluate the changes in this post-fracture treatment gap across three different countries from 2005 to 2015., Methods: This analysis, which is part of a multinational cohort study, included men and women, aged 50 years or older, sustaining a first incident fragility fracture. Using routinely collected patient data from three administrative health databases covering Catalonia, Denmark, and the United Kingdom, we estimated the treatment gap as the proportion of patients not treated with AOM within 1 year of their first incident fracture., Results: A total of 648,369 fracture patients were included. Mean age 70.2-78.9 years; 22.2-31.7% were men. In Denmark, the treatment gap was stable at approximately 88-90% throughout the 2005 to 2015 time period. In Catalonia, the treatment gap increased from 80 to 88%. In the UK, an initially decreasing treatment gap-though never smaller than 63%-was replaced by an increasing gap towards the end of our study. The gap was more pronounced in men than in women., Conclusion: Despite repeated calls for improved secondary fracture prevention, an unacceptably large treatment gap remains, with time trends indicating that the problem may be getting worse in recent years.

Objectives: There is uncertainty about when the first cases of COVID-19 appeared in Spain. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and estimate numbers of undetected COVID-19 cases., Design: Time-series study of influenza and COVID-19 cases, 2010-2020., Setting: Primary care, Catalonia, Spain., Participants: People registered in primary-care practices, covering >6 million people and >85% of the population., Main Outcome Measures: Weekly new cases of influenza and COVID-19 clinically diagnosed in primary care., Analyses: Daily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model expected case numbers with Auto Regressive Integrated Moving Average models, overall and stratified by age. Daily excess influenza cases were defined as the number of observed minus expected cases., Results: Four influenza season curves (2011-2012, 2012-2013, 2013-2014 and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 2020, 8017 (95% CI: 1841 to 14 718) excess influenza cases were identified. This excess was highest in the 15-64 age group., Conclusions: COVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. The use of clinical codes could misrepresent the true occurrence of the disease. Serological or PCR testing should be used to confirm these findings. In future, this surveillance of excess influenza could help detect new outbreaks of COVID-19 or other influenza-like pathogens, to initiate early public health responses., Competing Interests: Competing interests: DP-A reports grants and other from AMGEN; grants, non-financial support and other from UCB Biopharma; grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DP-A's department and open for external participants. AP-U reports grants from Fundacion Alfonso Martin Escudero and the Medical Research Council. No other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

This study aimed to determine if having an overweight or obese range body mass index (BMI) at time of beginning school is associated with increased fracture incidence in childhood. A dynamic cohort was created from children presenting for routine preschool primary care screening, collected in the Information System for Research in Primary Care (SIDIAP) platform in Catalonia, Spain. Data were collected from 296 primary care centers representing 74% of the regional pediatric population. A total of 466,997 children (48.6% female) with a validated weight and height measurement within routine health care screening at age 4 years (±6 months) between 2006 and 2013 were included, and followed up to the age of 15, migration out of region, death, or until December 31, 2016. BMI was calculated at age 4 years and classified using WHO growth tables, and fractures were identified using previously validated ICD10 codes in electronic primary care records, divided by anatomical location. Actuarial lifetables were used to calculate cumulative incidence. Cox regression was used to investigate the association of BMI category and fracture risk with adjustment for socioeconomic status, age, sex, and nationality. Median follow-up was 4.90 years (interquartile range [IQR] 2.50 to 7.61). Cumulative incidence of any fracture during childhood was 9.20% (95% confidence interval [CI] 3.79% to 14.61%) for underweight, 10.06% (9.82% to 10.29%) for normal weight, 11.28% (10.22% to 12.35%) for overweight children, and 13.05% (10.69% to 15.41%) for children with obesity. Compared with children of normal range weight, having an overweight and obese range BMI was associated with an excess risk of lower limb fracture (adjusted hazard ratio [HR] = 1.42 [1.26 to 1.59]; 1.74 [1.46 to 2.06], respectively) and upper limb fracture (adjusted HR = 1.10 [1.03 to 1.17]; 1.19 [1.07 to 1.31]). Overall, preschool children with an overweight or obese range BMI had increased incidence of upper and lower limb fractures in childhood compared with contemporaries of normal weight. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research., (© 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.)

The coordination of Fracture Liaison Services (FLS) with Primary Care (PC) is necessary for the continuity of care of patients with fragility fractures. This study proposes a Best Practice Framework (BPF) and performance indicators for the implementation and follow-up of FLS-PC coordination in clinical practice in Spain., Purpose: To develop a BPF for the coordination of FLS with PC in Spain and to improve the continuity of care for patients with fragility fractures., Methods: A Steering Committee selected experts from seven Spanish FLS and related PC doctors and nurses to participate in a best practice workshop. Selection criteria were an active FLS with an identified champion and prior contact with PC centres linked to the hospital. The main aim of the workshop was to review current FLS practices in Spain and their integration with PC. A BPF document with processes, tools, roles, and metrics was then generated., Results: Spanish FLS consists of a multidisciplinary team of physicians/nurses but with low participation of other professionals and PC staff. Evaluation and treatment strategies are widely variable. Four desired standards were agreed upon: (1) Effective channels for FLS-PC communication; (2) minimum contents of an FLS clinical report and its delivery to PC; (3) adherence monitoring 3 months after FLS baseline visit; and (4) follow-up by PC. Proposed key performance indicators are (a) number of FLS-PC communications, including consensus protocols; (b) confirmation FLS report received by PC; (c) medical/nursing PC appointment after FLS report received; and (d) number of training sessions in PC., Conclusions: The BPF provides a comprehensive approach for FLS-PC coordination in Spain, to promote the continuity of care in patients with fragility fractures and improve secondary prevention. The implementation of BPF recommendations and performance indicator tracking will benchmark best FLS practices in the future.

Introduction: In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK)., Participants: the database source populations were included for population-based analyses, and SR users for patient-level analyses., Intervention: New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy., Methods: Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016)., Results: The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4-62.9) in the reference to 8.5 (8.5-8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4-7.4) to 0.2 (0.2-0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period., Conclusions: Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

Type 2 diabetes mellitus (T2DM) is associated with an excess risk of fractures and overall mortality. This study compared hip fracture and post-hip fracture mortality in T2DM and non-diabetic subjects. The salient findings are that subjects in T2DM are at higher risk of dying after suffering a hip fracture., Introduction: Previous research suggests that individuals with T2DM are at an excess risk of both fractures and overall mortality, but their combined effect is unknown. Using multi-state cohort analyses, we estimate the association between T2DM and the transition to hip fracture, post-hip fracture mortality, and hip fracture-free all-cause death., Methods: Population-based cohort from Catalonia, Spain, including all individuals aged 65 to 80 years with a recorded diagnosis of T2DM on 1 January 2006; and non-T2DM matched (up to 2:1) by year of birth, gender, and primary care practice., Results: A total of 44,802 T2DM and 81,233 matched controls (53% women, mean age 72 years old) were followed for a median of 8 years: 23,818 died without fracturing and 3317 broke a hip, of whom 838 subsequently died. Adjusted HRs for hip fracture-free mortality were 1.32 (95% CI 1.28 to 1.37) for men and 1.72 (95% CI 1.65 to 1.79) for women. HRs for hip fracture were 1.24 (95% CI 1.08 to 1.43) and 1.48 (95% CI 1.36 to 1.60), whilst HRs for post-hip fracture mortality were 1.28 (95% CI 1.02 to 1.60) and 1.57 (95% CI 1.31 to 1.88) in men and women, respectively., Conclusion: T2DM individuals are at increased risk of hip fracture, post-hip fracture mortality, and hip fracture-free death. After adjustment, T2DM men were at a 28% higher risk of dying after suffering a hip fracture and women had 57% excess risk of post-hip fracture mortality.

Objective: Rheumatoid factor (RF) testing is used in primary care in the diagnosis of rheumatoid arthritis (RA); however a positive RF may occur without RA. Incorrect use of RF testing may lead to increased costs and delayed diagnoses. The aim was to assess the performance of RF as a test for RA and to estimate the costs associated with its use in a primary care setting., Material and Methods: A retrospective cohort study using the Information System for the Development of Research in Primary Care database (contains primary care records and laboratory results of >80% of the Catalonian population, Spain). Participants were patients ≥18 years with ≥1 RF test performed between 01/01/2006 and 31/12/2011, without a pre-existing diagnosis of RA. Outcome measures were an incident diagnosis of RA within 1 year of testing, and the cost of testing per case of RA., Results: 495,434/4,796,498 (10.3%) patients were tested at least once. 107,362 (21.7%) of those tested were sero-positive of which 2768 (2.6%) were diagnosed with RA within 1 year as were 1141/388,072 (0.3%) sero-negative participants. The sensitivity of RF was 70.8% (95% CI 69.4-72.2), specificity 78.7% (78.6-78.8), and positive and negative predictive values 2.6% (2.5-2.7) and 99.7% (99.6-99.7) respectively. Approximately €3,963,472 was spent, with a cost of €1432 per true positive case., Conclusions: Although 10% of patients were tested for RF, most did not have RA. Limiting testing to patients with a higher pre-test probability would significantly reduce the cost of testing., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objective: The aim of this study was to estimate lifetime risk of knee and hip replacement following a GP diagnosis of osteoarthritis and assess how this risk varies with patient characteristics., Methods: Routinely collected data from Catalonia, Spain, covering 2006 to 2015, were used. Study participants had a newly recorded GP diagnosis of knee or hip osteoarthritis. Parametric survival models were specified for risk of knee/hip replacement and death following diagnosis. Survival models were combined using a Markov model and lifetime risk estimated for the average patient profile. The effects of age at diagnosis, sex, comorbidities, socioeconomic status, body mass index (BMI), and smoking on risk were assessed., Results: 48,311 individuals diagnosed with knee osteoarthritis were included, of whom 2,561 underwent knee replacement. 15,105 individuals diagnosed with hip osteoarthritis were included, of whom 1,247 underwent hip replacement. The average participant's lifetime risk for knee replacement was 30% (95% CI: 25-36%) and for hip replacement was 14% (10-19%). Notable patient characteristics influencing lifetime risk were age at diagnosis for knee and hip replacement, sex for hip replacement, and BMI for knee replacement. BMI increasing from 25 to 35 was associated with lifetime risk of knee replacement increasing from 24% (20-28%) to 32% (26-37%) for otherwise average patients., Conclusion: Knee and hip replacement are not inevitable after an osteoarthritis diagnosis, with average lifetime risks of less than a third and a sixth, respectively. Patient characteristics, most notably BMI, influence lifetime risks., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking., Aim: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout., Methods: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAP Q ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score., Results: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63)., Conclusions: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.

Objective: The Spanish National Hip Fracture Registry (Registro Nacional de Fracturas de Cadera or RNFC) is a Spanish, prospective, multi- centric registry, commenced in 2017. The goal of this paper is to present the data from the first annual report and to compare them with autonomic registries and recent prospective multi-centric studies performed in Spain., Methods: We included persons 75 years or older treated for fragility hip fractures in any of the centers participating in the RNFC between January and October 2017. The descriptive statistics of each variable used the mean (and standard deviation) or the median (and interquartile ranges) for the ordinal variables and the percentage for the categoric variables. A descriptive analysis of the casemix was performed and compared with available data from the aforementioned studies., Results: The RNFC included 7.208 patients from 54 hospitals, with a mean age of 86.7 (SD 5.6) years; 75.4% were women, and 36.4% showed cognitive decline. Mean surgical delay was 75.7 (SD 63.6) hours, and length of stay averaged 10.9 (SD 6.7) days. Of the patients who lived at home (75.4%), less than half (37.0%) returned home at discharge. One-month mortality was 7.1%. Comparison with other studies showed important differences, especially regarding patients newly sent to nursing homes (7.7-29.4%) and with antiosteoporotic treatment at discharge (14.5-36.7%)., Conclusions: The RNFC is the largest prospective database to date that offers data regarding the characteristics of patients hospitalized for hip fractures in Spain. Comparison with recent studies showed some important differences., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Electronic medical records databases use pre-specified lists of diagnostic codes to identify fractures. These codes, however, are not specific enough to disentangle traumatic from fragility-related fractures. We report on the proportion of fragility fractures identified in a random sample of coded fractures in SIDIAP., Methods: Patients≥50 years old with any fracture recorded in 2012 (as per pre-specified ICD-10 codes) and alive at the time of recruitment were eligible for this retrospective observational study in 6 primary care centres contributing to the SIDIAP database (www.sidiap.org). Those with previous fracture/s, non-responders, and those with dementia or a serious psychiatric disease were excluded. Data on fracture type (traumatic vs fragility), skeletal site, and basic patient characteristics were collected., Results: Of 491/616 (79.7%) patients with a registered fracture in 2012 who were contacted, 331 (349 fractures) were included. The most common fractures were forearm (82), ribs (38), and humerus (32), and 225/349 (64.5%) were fragility fractures, with higher proportions for classic osteoporotic sites: hip, 91.7%; spine, 87.7%; and major fractures, 80.5%. This proportion was higher in women, the elderly, and patients with a previously coded diagnosis of osteoporosis., Conclusions: More than 4 in 5 major fractures recorded in SIDIAP are due to fragility (non-traumatic), with higher proportions for hip (92%) and vertebral (88%) fracture, and a lower proportion for fractures other than major ones. Our data support the validity of SIDIAP for the study of the epidemiology of osteoporotic fractures., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Hip fracture registries have helped improve quality of care and reduce variability, and several audits exist worldwide. The results of the Spanish National Hip Fracture Registry are presented and compared with 13 other national registries, highlighting similarities and differences to define areas of improvement, particularly surgical delay and early mobilization., Introduction: Hip fracture audits have been useful for monitoring current practice and defining areas in need of improvement. Most established registries are from Northern Europe. We present the results from the first annual report of the Spanish Hip Fracture Registry (RNFC) and compare them with other publically available audit reports., Method: Comparison of the results from Spain with the most recent reports from another ten established hip fracture registries highlights the differences in audit characteristics, casemix, management, and outcomes., Results: Of the patients treated in 54 hospitals, 7.208 were included in the registry between January and October 2017. Compared with other registries, the RNFC included patients ≥ 75 years old; in general, they were older, more likely to be female, had a worse prefracture ambulation status, and were more likely to have extracapsular fractures. A larger proportion was treated with intramedullary nails than in other countries, and spinal anesthesia was most commonly used. With a mean of 75.7 h, Spain had by far the longest surgical delay, and the lowest proportion of patients mobilized on the first postoperative day (58.5%). Consequently, development of pressure ulcers was high, but length of stay, mortality, and discharge to home remained in the range of other audits., Conclusions: National hip fracture registries have proved effective in changing clinical practice and our understanding of patients with this condition. Such registries tend to be based on an internationally recognized common dataset which would make comparisons between national registries possible, but variations such as age inclusion criteria and follow-up are becoming evident across the world. This variation should be avoided if we are to maximize the comparability of registry results and help different countries learn from each other's practice. The results reported in the Spanish RNFC, compared with those of other countries, highlight the differences between countries and detect areas of improvement, particularly surgical delay and early mobilization.

Purpose: The medical morbidity and mortality associated with neck of femur fractures is well-documented, whereas there is limited data for patient-reported outcomes. The aim of this study was to characterize the impact of neck of femur fractures on activities of daily living and patient-reported health-related quality of life., Methods: Design and participants: Multicentric prospective cohort study. Consecutive sample patients with fragility hip fracture over 50 years old admitted in 48 hospitals in Spain., Outcomes: daily living activity function (Barthel Index) and health-related quality of life (EQ-5D) pre-fracture, admission to hospital and at 1- and 4-month follow-up post-fracture., Statistics: Barthel and EQ-5D over time are described as mean (SD) and median (interquartile range)., Results: A total of 997 patients were recruited at baseline with 4-month outcomes available for, and 856 patients (89.5%). Barthel Index fell from 78.77 (23.75) at baseline to 43.62 (19.86) on admission to hospital with the fracture. Scores partially recovered to 54.89 (25.40) and 64.09 (21.35) at 1- and 4-month post-fracture, respectively. EQ-5D fell from a median of 0.75 (0.47-0.91) to - 0.01 (- 0.03 to 0.51) on admission. Partial recovery was observed again to (0.51 (- 0.06 to 0.67)) and (0.60 (0.10 to 0.80)) at 1- and 4-month post-fracture, respectively., Conclusions: Hip fracture results in a large decline in the ability to perform activities of daily living and patient-reported health-related quality of life with only partial recovery amongst survivors 4-month post-fracture.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Here we used healthcare records of 18 million adults to estimate risk of acquiring advanced liver disease diagnoses in patients with NAFLD or NASH compared to individually matched controls., Methods: Data were extracted from four European primary care databases representing the UK, Netherlands, Italy and Spain. Patients with a recorded diagnosis of NAFLD or NASH (NAFLD/NASH) were followed up for incident cirrhosis and HCC diagnoses. Each coded NAFLD/NASH patient was matched to up to 100 "non-NAFLD" patients by practice site, gender, age ± 5 years and visit recorded within ± 6 months. Hazard ratios (HR) were estimated using Cox models adjusted for age and smoking status and pooled across databases by random effects meta-analyses., Results: Out of 18,782,281 adults, we identified 136,703 patients with coded NAFLD/NASH. Coded NAFLD/NASH patients were more likely to have diabetes, hypertension and obesity than matched controls. HR for cirrhosis in patients compared to controls was 4.73 (95% CI 2.43-9.19) and for HCC, 3.51 (95% CI 1.72-7.16). HR for either outcome was higher in patients with NASH and those with high-risk Fib-4 scores. The strongest independent predictor of a diagnosis of HCC or cirrhosis was baseline diagnosis of diabetes., Conclusions: Real-world population data show that recorded diagnosis of NAFLD/NASH increases risk of life-threatening liver outcomes. Diabetes is an independent predictor of advanced liver disease diagnosis, emphasising the need to identify specific groups of patients at highest risk.

We have characterised 997 hip fracture patients from a representative 45 Spanish hospitals, and followed them up prospectively for up to 4 months. Despite suboptimal surgical delays (average 59.1 hours), in-hospital mortality was lower than in Northern European cohorts. The secondary fracture prevention gap is unacceptably high at 85%., Purpose: To characterise inpatient care, complications, and 4-month mortality following a hip or proximal femur fracture in Spain., Methods: Design: prospective cohort study. Consecutive sample of patients ≥ 50 years old admitted in a representative 45 hospitals for a hip or proximal femur fragility fracture, from June 2014 to June 2016 and followed up for 4 months post-fracture. Patient characteristics, site of fracture, in-patient care (including secondary fracture prevention) and complications, and 4-month mortality are described., Results: A total of 997 subjects (765 women) of mean (standard deviation) age 83.6 (8.4) years were included. Previous history of fracture/s (36.9%) and falls (43%) were common, and 10-year FRAX-estimated major and hip fracture risks were 15.2% (9.0%) and 8.5% (7.6%) respectively. Inter-trochanteric (44.6%) and displaced intra-capsular (28.0%) were the most common fracture sites, and fixation with short intramedullary nail (38.6%) with spinal anaesthesia (75.5%) the most common procedures. Surgery and rehabilitation were initiated within a mean 59.1 (56.7) and 61.9 (55.1) hours respectively, and average length of stay was 11.5 (9.3) days. Antithrombotic and antibiotic prophylaxis were given to 99.8% and 98.2% respectively, whilst only 12.4% received secondary fracture prevention at discharge. Common complications included delirium (36.1 %) and kidney failure (14.1%), with in-hospital and 4-month mortality of 2.1% and 11% respectively., Conclusions: Despite suboptimal surgical delay, post-hip fracture mortality is low in Spanish hospitals. The secondary fracture prevention gap is unacceptably high at > 85%, in spite of virtually universal anti-thrombotic and antibiotic prophylaxis.

Background: An increased fracture risk has been described as a complication of Type 2 diabetes mellitus (T2DM). Clinical prediction models for general population have a limited predictive accuracy for fractures in T2DM patients. The aim was to develop and validate a clinical prediction tool for the estimation of 5-year hip and major fracture risk in T2DM patients., Methods and Results: A cohort of newly diagnosed T2DM patients (n = 51,143, aged 50-85, 57% men) was extracted from the Information System for the Development of Research in Primary Care (SIDIAP) database, containing computerized primary care records for >80% of the population of Catalonia, Spain (>6 million people). Patients were followed up from T2DM diagnosis until the earliest of death, transfer out, fracture, or end of study. Cox proportional hazards regression was used to model the 5-year risk of hip and major fracture. Calibration and discrimination were assessed. Hip and major fracture incidence rates were 1.84 [95%CI 1.64 to 2.05] and 7.12 [95%CI 6.72 to 7.53] per 1,000 person-years, respectively. Both hip and major fracture prediction models included age, sex, previous major fracture, statins use, and calcium/vitamin D supplements; previous ischemic heart disease was also included for hip fracture and stroke for major fracture. Discrimination (0.81 for hip and 0.72 for major fracture) and calibration plots support excellent internal validity., Conclusions: The proposed prediction models have good discrimination and calibration for the estimation of both hip and major fracture risk in incident T2DM patients. These tools incorporate key T2DM macrovascular complications generally available in primary care electronic medical records, as well as more generic fracture risk predictors. Future work will focus on validation of these models in external cohorts., Competing Interests: We have the following interests: DML has received support from FEIOMM (Bone Research Spanish Foundation) for the submitted work; DML has received personal fees from Eli Lilly, Amgen, and Novartis; CT has received lecture and personal fees from Boehringer Ingelheim; CC has received personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Les Laboratoires Servier, Takeda and UCB; DPA has received grant support from Amgen, Les Laboratoires Servier, and UCB Pharma SRL related to other projects; DPA has previously consulted for UCB Pharma SRL; DPA has received lecture fees from Amgen; XN, MKJ, VM, ADP, and GSC have nothing to declare. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy., Introduction: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions., Methods: A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator)., Results: Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications., Conclusions: Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Type 2 diabetes (T2DM) is associated with a reduced life expectancy. The latest published evidence suggests an increased risk of fractures among T2DM patients. We conducted a population-based cohort study to determine the impact of mortality as a competing risk in the study of the association between T2DM and hip fracture rates. Participants were all diagnosed T2DM patients registered in the Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) database aged 65 years and older; up to two non-T2DM were matched by age, sex, and primary care facility. We used Cox regression models to estimate cause-specific hazard ratio (HR) of death or hip fracture according to T2DM status. Fine and Gray models were then fitted to estimate the subhazard ratio (SHR) of hip fracture while accounting for competing risk with death and to estimate the probability of hip fracture within 5 years. A total of 55,891 T2DM and 103,093 matched non-T2DM patients were observed for a median of 8 years. Mortality was 48.8 per 1000 person years (py) in T2DM, and 33.8 per 1000 py in non-T2DM; hip fracture rates were 6.0 per 1000 py and 4.9 per 1000 py, respectively. Cox models confirmed a significant association for death and hip fracture: HR 1.51 (95% CI, 1.48 to 1.55), and HR 1.32 (95% CI, 1.24 to 1.40), respectively. Accounting for death as a competing event (Fine-Gray models), the association between T2DM and hip fracture risk remained statistically significant (SHR 1.15; 95% CI, 1.09 to 1.21) and the probability of a hip fracture within 5 years was 2.3% for TD2M and 1.9% for non-TD2M patients compared to 2.6% and 2.1% respectively using Kaplan-Meier (KM) estimates. T2DM patients have a 50% increased mortality and, after adjusting for differential survival at 5 years, a 21% increased incidence of hip fracture when compared to matched non-T2DM. Failing to account for differential mortality leads to an overestimation of fracture risk. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Objective: To ascertain the current situation and clinical variability of the provision of care for Hip Fracture (HF) in Spain and the factors related to it by using a National Registry (NHFR) with high patient numbers and territorial representation NHFR, and to compare results on a national and international level and propose standards and criteria to improve healthcare quality., Design: Continuous registry for at least three years of a representative sample of patients admitted to Spanish hospitals due to HF using the Minimum Common Dataset - international Fragility Fracture Network (FFN) MCD, adapted for Spanish. STUDY SCOPE AND SUBJECTS: all patients over the age of 74 years who are hospitalized with a diagnosis of a fragility HF at the participating hospitals distributed throughout the Spanish territory. Initially 48 hospitals are included, and we expect to incorporate the highest number of sites possible., Results: It is expected to ascertain the current situation of provision of care for HF in Spain. Each hospital will be offered information regarding their results and their situation compared to the rest. The results from national hospitals will be compared to others included in the registry and to hospitals abroad, which use the same database. Variability will be studied, care standards will be established, and objectives will be proposed for the continuous improvement of the care process of this condition., (Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94-1.18) and 0.96 (0.78-1.18)], strontium [0.90 (0.61-1.34) and 1.19 (0.82-1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25-12.66)] and teriparatide [1.27 (0.59-2.71)] in Spain, did not differ versus alendronate., Introduction: Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy)., Methods: Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000-2014 (CPRD) or 2001-2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used., Results: Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94-1.18) and 0.96 (0.78-1.18) for other bisphosphonates, and 0.90 (0.61-1.34) and 1.19 (0.82-1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25-12.66) for denosumab and 1.27 (0.59-2.71) for teriparatide in BIFAP., Conclusions: VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.

The aim of this study was to assess the prevalence of densitometric osteoporosis and vertebral fractures in Spanish men aged ≥50 years, and to study how the relationship between them may change depending on how osteoporosis is diagnosed. A community-based population of 1003 men aged ≥50 years was studied. Bone mineral density (BMD) was measured by DXA at the lumbar spine, femoral neck and total hip. Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs. The prevalence of osteoporosis was estimated with both the World Health Organization (WHO) (T-score of <-2.5 at the femoral neck, calculated using the young white female normal reference database) and the National Osteoporosis Foundation (NOF) criteria (T-score of <-2.5 at the femoral neck, total hip or lumbar spine, calculated using the young white male normal reference database). The prevalence of osteoporosis using the WHO criterion was 1.1% and using the NOF criterion was 13%, while that of vertebral fractures was 21.3%. The area under the curve (AUC) for the relationship between BMD and vertebral fracture prevalence was 0.64. The odds ratio for osteoporosis using the WHO definition was 2.57 (p = 0.13), and 1.78 (p = 0.007) using the NOF definition. Vertebral fracture prevalence rose with age. The prevalence of osteoporosis increased only moderately in men aged >70 years with the WHO criterion, and showed no change using the NOF definition. The prevalence of osteoporosis in Spanish men using the WHO definition is too small to have any meaningful clinical use. Although the figure is higher using the NOF definition, it would seem that population-based studies of BMD in men are of questionable value.

Despite normal to high bone mineral density, patients with type 2 diabetes (T2DM) have an increased fracture risk. T2DM medications could partially account for this excess risk. The aim of this study was to assess the association between insulin use and bone fracture risk in T2DM patients. A population-based matched cohort study based on a primary care records database validated for research use (Catalonia, Spain) was performed. Propensity score (PS) for insulin use was calculated using logistic regression including predefined predictors of fractures. A total of 2,979 insulin users and 14,895 non-users were observed for a median of 1.42 and 4.58 years respectively. Major fracture rates were 11.2/1,000 person-years for insulin users, compared with 8.3/1,000 among non-users. Matched models confirmed a significant association, with an adjusted subhazard ratio (adj SHR) of 1.38 [95% CI 1.06 to 1.80] for major fractures. No differences between types of insulin or different regimens were found. Estimated number needed to harm (fracture) was 82 (95% CI 32 to 416). Insulin use appears to be associated with a 38% excess fracture risk among T2DM patients in the early stages of the disease. Fracture risk should be included among the considerations to initiate insulin treatment.

Objective: It is unclear what impact obesity has on the progression of knee osteoarthritis (OA) from diagnosis to knee replacement surgery. This study was undertaken to examine the relative risk of knee replacement surgery in overweight and obese patients who were newly diagnosed as having knee OA in a community setting., Methods: Subjects were selected from the Information System for Development of Primary Care Research database, which compiles comprehensive clinical information collected by health care professionals for >5.5 million people in Catalonia, Spain (80% of the population). Patients newly diagnosed as having knee OA in primary care between 2006 and 2011 were included. Knee replacement was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification codes from linked hospital admissions data. Multivariable Cox regression models were fitted for knee replacement according to body mass index (BMI), and were adjusted for relevant confounders. Population proportional attributable risk was calculated., Results: A total of 105,189 participants were followed up for a median of 2.6 years (interquartile range 1.3-4.2). Of these patients, 7,512 (7.1%) underwent knee replacement. Adjusted hazard ratios and 95% confidence intervals (95% CIs) for knee replacement for the World Health Organization BMI categories were 1.41 (95% CI 1.27-1.57) for overweight, 1.97 (95% CI 1.78-2.18) for obese I, 2.39 (95% CI 2.15-2.67) for obese II, and 2.67 (95% CI 2.34-3.04) for obese III compared to normal weight. The effect of BMI on risk of knee replacement was stronger among younger participants. The population attributable risk of obesity for knee OA-related knee replacement was 31.0%., Conclusion: Overweight and obese patients are at >40% and 100% increased risk of knee replacement surgery, respectively, compared to patients with normal weight. This association is even stronger in younger patients. Weight reduction strategies could potentially reduce the need for knee replacement surgery by 31% among patients with knee OA., (© 2016, American College of Rheumatology.)

Although a number of reports suggest very low persistence with oral bisphosphonates, there is limited data on persistence with other anti-osteoporosis medications. We compare rates of early discontinuation (in the first year) with all available outpatient anti-osteoporosis drugs in Catalonia, Spain. We conducted a population-based retrospective cohort study using data from the SIDIAP database. SIDIAP contains computerized primary care records and pharmacy dispensing data for >80 % of the population of Catalonia (>5 million people). All SIDIAP participants starting an anti-osteoporosis drug between 1/1/2007 and 30/06/2011 (with 2 years wash-out) were included. We modelled persistence as the time between first prescription and therapy discontinuation (refill gap of at least 6 months) using Fine and Gray survival models with competing risk for death. We identified 127,722 patients who started any anti-osteoporosis drug in the study period. The most commonly prescribed drug was weekly alendronate (N = 55,399). 1-Year persistence ranges from 40 % with monthly risedronate to 7.7 % with daily risedronate, and discontinuation was very common [from 49.5 % (monthly risedronate) to 84.4 % (daily risedronate)] as was also switching in the first year of therapy [from 2.8 % (weekly alendronate) to 10 % (daily alendronate)]. Multivariable-adjusted models showed that only monthly risedronate had better one-year persistence than weekly alendronate and teriparatide equivalent, whilst all other therapies had worse persistence. Early discontinuation with available anti-osteoporosis oral drugs is very common. Monthly risedronate, weekly alendronate, and daily teriparatide are the drugs with the best persistence, whilst daily oral drugs have 40-60 % higher first-year discontinuation rates compared to weekly alendronate.

Objective: To determine the association between socio-economic status (SES) and risk of hand, hip or knee osteoarthritis (OA) at a population level., Design: Retrospective ecological study using the System for the Development of Research in Primary Care (SIDIAP) database (primary care anonymized records for >5 million people in Catalonia (Spain)). Urban residents >15 years old (2009-2012) were eligible., Outcomes: Validated area-based SES deprivation index MEDEA (proportion of unemployed, temporary workers, manual workers, low educational attainment and low educational attainment among youngsters) was estimated for each area based on census data as well as incident diagnoses (ICD-10 codes) of hand, hip or knee OA (2009-2012). Zero-inflated Poisson models were fitted to study the association between MEDEA quintiles and the outcomes., Results: Compared to the least deprived, the most deprived areas were younger (43.29 (17.59) vs 46.83 (18.49), years (Mean SD), had fewer women (49.1% vs 54.8%), a higher percentage of obese (16.2% vs 8.4%), smokers (16.9% vs 11.9%) and high-risk alcohol consumption subjects (1.5% vs 1.3%). Compared to the least deprived, the most deprived areas had an excess risk of OA: age-sex-adjusted Incidence Rate Ratio (IRR) 1.26 (1.11-1.42) for hand, 1.23 (1.17-1.29) hip, and 1.51 (1.45-1.57) knee. Adjustment for obesity attenuated this association: 1.06 (0.93-1.20), 1.04 (0.99-1.09), and 1.23 (1.19-1.28) respectively., Conclusions: Deprived areas have higher rates OA (hand, hip, knee). Their increased prevalence of obesity accounts for a 50% of the excess risk of knee OA observed. Public health interventions to reduce the prevalence of obesity in this population could reduce health inequalities., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients with OA use different drugs in their search for relief. We aimed to study the prevalence of use and combinations of different medications for OA in a population-based cohort of OA patients in Catalonia, Spain, while characterizing users of each of the drugs available, with a particular focus on cardiovascular risk factors., Methods: Data were obtained from the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) database, which includes electronic medical records and pharmacy invoice data for >5 million people from Catalonia. Study participants were those with a clinical diagnosis of OA in 2006-10. Drugs studied included oral and topical NSAIDs, analgesics (paracetamol, metamizole), opioids (tramadol, fentanyl), cyclooxygenase 2 (COX-2) inhibitors and symptomatic slow-acting drugs in OA. Drug utilization was described using medication possession ratios (MPRs), equivalent to the proportion of days covered with the drug of interest. The annual incidence of new users in the first year after OA diagnosis from 2006 to 2010 was estimated for all studied drugs among newly diagnosed OA patients using Poisson regression., Results: We identified 238 536 study participants. The most common regimen of treatment consisted of at least three drugs (53.9% of patients). The drugs most frequently used regularly (MPR ≥50%) were chondroitin (21.2%), glucosamine (15.8%) and oral NSAIDs (14.4%). The incidence of the use of opioids, COX-2 inhibitors and chondroitin increased over the 5 year period, whereas all others decreased., Conclusion: Drug combinations are common in the treatment of OA patients, who are thus exposed to potential drug interactions, with unknown impacts on their health. The increasing use of opioids and COX-2 inhibitors is noteworthy because of the potential impact on safety and costs., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Summary: There is scarce data on the association between early stages of type 2 diabetes and fracture risk. We report a 20% excess risk of hip fracture in the first years following disease onset compared to matched non-diabetic patients., Introduction: Type 2 diabetes mellitus (T2DM) is a chronic disease that affects several target organs. Data on the association between T2DM and osteoporotic fractures is controversial. We estimated risk of hip fracture in newly diagnosed T2DM patients, compared to matched non-diabetic peers., Methods: We conducted a population-based parallel cohort study using data from the Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP) database. Participants were all newly diagnosed T2DM patients registered in SIDIAP in 2006-2011 (T2DM cohort). Up to two diabetes-free controls were matched to each T2DM participant on age, gender, and primary care practice. Main outcome was incident hip fracture in 2006-2011, ascertained using the tenth edition of the International Classification of Diseases (ICD-10) codes. We used Fine and Gray survival modelling to estimate risk of hip fracture according to T2DM status, accounting for competing risk of death. Multivariate models were adjusted for body mass index, previous fracture, and use of oral corticosteroids., Results: During the study period (median follow-up 2.63 years), 444/58,483 diabetic patients sustained a hip fracture (incidence rate 2.7/1,000 person-years) compared to 776/113,448 matched controls (2.4/1,000). This is equivalent to an unadjusted (age- and gender-matched) subhazard ratio (SHR) 1.11 [0.99-1.24], and adjusted SHR 1.20 [1.06-1.35]. The adjusted SHR for major osteoporotic and any osteoporotic fractures were 0.95 [0.89-1.01] and 0.97 [0.92-1.02]., Conclusions: Newly diagnosed T2DM patients are at a 20% increased risk of hip fracture even in early stages of disease, but no for all fractures. More data is needed on the causes for an increased fracture risk in T2DM patients as well as on the predictors of osteoporotic fractures among these patients.

Background: Area-based measures of economic deprivation are seldom applied to large medical records databases to establish population-scale associations between deprivation and disease., Objective: To study the association between deprivation and incidence of common cancer types in a Southern European region., Methods: Retrospective ecological study using the SIDIAP (Information System for the Development of Research in Primary Care) database of longitudinal electronic medical records for a representative population of Catalonia (Spain) and the MEDEA index based on urban socioeconomic indicators in the Spanish census. Study outcomes were incident cervical, breast, colorectal, prostate, and lung cancer in 2009-2012. The completeness of SIDIAP cancer recording was evaluated through linkage of a geographic data subset to a hospital cancer registry. Associations between MEDEA quintiles and cancer incidence was evaluated using zero-inflated Poisson regression adjusted for sex, age, smoking, alcoholism, obesity, hypertension, and diabetes., Results: SIDIAP sensitivity was 63% to 92% for the five cancers studied. There was direct association between deprivation and lung, colorectal, and cervical cancer: incidence rate ratios (IRR) 1.82 [1.64-2.01], IRR 1.60 [1.34-1.90], IRR 1.22 [1.07-1.38], respectively, comparing the most deprived to most affluent areas. In wealthy areas, prostate and breast cancers were more common: IRR 0.92 [0.80-1.00], IRR 0.91 [0.78-1.06]. Adjustment for confounders attenuated the association with lung cancer risk (fully adjusted IRR 1.16 [1.08-1.25]), reversed the direction of the association with colorectal cancer (IRR 0.90 [0.84-0.95]), and did not modify the associations with cervical (IRR 1.27 [1.11-1.45]), prostate (0.74 [0.69-0.80]), and breast (0.76 [0.71-0.81]) cancer., Conclusions: Deprivation is associated differently with the occurrence of various cancer types. These results provide evidence that MEDEA is a useful, area-based deprivation index for analyses of the SIDIAP database. This information will be useful to improve screening programs, cancer prevention and management strategies, to reach patients more effectively, particularly in deprived urban areas.