Risk of Ischemic Stroke Associated with Calcium Supplements and Interaction with Oral Bisphosphonates: A Nested Case-Control Study.

Conflicting results about the association of calcium supplements (CS) with ischemic stroke (IS) have been reported. We tested this hypothesis by differentiating between CS alone (CaM) and CS with vitamin D (CaD) and between cardioembolic and non-cardioembolic IS. We examined the potential interaction with oral bisphosphonates (oBs). A nested case-control study was carried out. We identified incident IS cases aged 40-90 and randomly sampled five controls per case matched by age, sex, and index date. Current users were compared to non-users. An adjusted odds ratios (AOR) and 95% CI were computed through conditional logistic regression. Only new users were considered. We included 13,267 cases (4400 cardioembolic, 8867 non-cardioembolic) and 61,378 controls (20,147 and 41,231, respectively). CaM use was associated with an increased risk of cardioembolic IS (AOR = 1.88; 95% CI: 1.21-2.90) in a duration-dependent manner, while it showed no association with non-cardioembolic IS (AOR = 1.05; 95% CI: 0.74-1.50); its combination with oBs increased the risk of cardioembolic IS considerably (AOR = 2.54; 95% CI: 1.28-5.04), showing no effect on non-cardioembolic. CaD use was not associated with either cardioembolic (AOR = 1.08; 95% CI: 0.88-1.31) or non-cardioembolic IS (AOR = 0.98; 95% CI: 0.84-1.13) but showed a small association with cardioembolic IS when combined with oBs (AOR = 1.35; 95% CI: 1.03-1.76). The results support the hypothesis that CS increases the risk of cardioembolic IS, primarily when used concomitantly with oBs.

Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study.

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82-1.49; AOR>1-3 years = 1.41; 95% CI:1.01-1.97; AOR>3 years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Risk of ischaemic stroke among new users of glucosamine and chondroitin sulphate: a nested case-control study.

Background: Several studies have reported that the use of chondroitin sulphate (CS) and glucosamine may reduce the risk of acute myocardial infarction. Although it is thought that this potential benefit could be extended to ischaemic stroke (IS), the evidence is scarce. Objective: To test the hypothesis that the use of prescription glucosamine or CS reduces the risk of IS. Design: Case-control study nested in an open cohort. Methods: Patients aged 40-99 years registered in a Spanish primary healthcare database (BIFAP) during the 2002-2015 study period. From this cohort, we identified incident cases of IS, applying a case-finding algorithm and specific validation procedures, and randomly sampled five controls per case, individually matched with cases by exact age, gender and index date. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of glucosamine or CS were considered. Results: A total of 13,952 incident cases of IS and 69,199 controls were included. Of them, 106 cases (0.76%) and 803 controls (1.16%) were current users of glucosamine or CS at index date, yielding an AOR of 0.66 (95% CI: 0.54-0.82) (for glucosamine, AOR: 0.55; 95% CI: 0.39-0.77; and for CS, AOR: 0.77; 95% CI: 0.60-0.99). The reduced risk among current users was observed in both sexes (men, AOR: 0.69; 95% CI: 0.49-0.98; women, AOR: 0.65; 95% CI: 0.50-0.85), in individuals above and below 70 years of age (AOR: 0.69; 95% CI: 0.53-0.89 and AOR: 0.59; 95% CI: 0.41-0.85, respectively), in individuals with vascular risk factors (AOR: 0.53; 95% CI: 0.39-0.74) and among current/recent users of nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR: 0.71; 95% CI: 0.55-0.92). Regarding duration, the reduced risk was observed in short-term users (<365 days, AOR: 0.61; 95% CI: 0.48-0.78) while faded and became nonsignificant in long-term users (>364 days AOR: 0.86; 95% CI: 0.57-1.31). Conclusions: Our results support a protective effect of prescription CS and glucosamine in IS, which was observed even in patients at vascular risk. Mini abstract: Our aim was to analyse whether the use of glucosamine or chondroitin sulphate (CS) reduces the risk of ischaemic stroke (IS). We detected a significant decrease.

Trends in orthopaedic surgery for spondyloarthritis: outcomes from a National Hospitalised Patient Registry (MBDS) over a 17-year period (1999-2015).TREND-EspA study.

OBJECTIVE: To assess the incidence of orthopaedic surgery (OS) (including total hip arthroplasty (THA), total knee arthroplasty, upper limb arthroplasty, arthrodesis and spinal surgery) and associated trends in patients with spondyloarthritis (SpA) over a long period (17 years). METHODS: An observational, retrospective, population-based, serial cross-sectional study was conducted. All hospital admissions of patients with SpA reported between 1999 and 2015 were analysed, and a control group was selected and matched by age, sex and year of admission. Incidence rates for OS (and subtypes) were calculated. Generalised linear models were used to analyse trends; unconditional logistic regression models were used to calculate crude and adjusted ORs (aORs) with the aim of evaluating the association between OS and SpA. RESULTS: The study database contained data on 214 280 hospital admissions (SpA/non-SpA 1:1 ratio). In the SpA cohort, 5 382 admissions (5.02%) had undergone OS compared with 3 533 in the non-SpA cohort (3.29%) (AOR 1.64; 95% CI 1.57 to 1.72). OS rates increased for both cohorts (+4.92% per year vs +8.41%). The trend in OS, THA, arthrodesis and spinal surgery decreased or stabilised in patients under age 60 in the SpA cohort, while the non-SpA cohort remained stable. In the SpA cohort, the mean age was 53.68 years (SD 13.65) in 1999, increasing to 62.76 years (SD 12.74) in 2015. In the non-SpA cohort, the mean age remained stable at around 63 years. CONCLUSIONS: A 9-year difference in the age of patients undergoing OS was observed in patients with SpA. The incidence of OS, THA and arthrodesis decreased in patients under age 60, and the incidence of spinal surgery decreased in patients under age 40. Our findings suggest that these patients are increasingly able to defer surgical interventions.

Association of spondyloarthritis and sarcoidosis: A retrospective observational population-based matched cohort study.

OBJECTIVES: To investigate the association between spondyloarthritis (SpA) and sarcoidosis. METHODS: An observational retrospective population-based matched cohort study was conducted. Using data from the Spanish Minimum Basic Data Set. All the admissions of patients with SpA reported between 1999 and 2015 were analysed and a control group matched by age, sex and year of admission was selected. Crude and age- and sex-adjusted incidence rates for sarcoidosis were calculated. Generalized linear models were used for trend analysis and unconditional logistic regression models for calculating crude and adjusted odds ratios (ORs) to assess the association between sarcoidosis and SpA. RESULTS: The study database contained data on 214,280 hospitalisations: 107,140 admissions of patients with SpA and 107,140 of patients without SpA. Overall, 220 of the admissions were of patients with sarcoidosis: 133 (0.12%) in the SpA group and 87 (0.08%) in the non-SpA group (P<0.05). The incidence rates of sarcoidosis were 2.68 and 1.64 per 100,000 per year in the SpA and non-SpA groups, respectively. The trend was similar in the two cohorts. Regarding potential associations between SpA and sarcoidosis, the crude and adjusted ORs were 1.52 (95% CI: 1.16-2.01) and 1.50 (95% CI: 1.14-1.97) overall in patients with SpA, with adjusted ORs of 1.42 (95% CI: 1.03-1.94) and 1.81 (95% CI: 1.29-2.55) in patients with ankylosing spondylitis and psoriatic arthritis, respectively. CONCLUSIONS: There is a relationship that is not due to chance between sarcoidosis and SpA and specifically that sarcoidosis is significantly associated with ankylosing spondylitis and psoriatic arthritis.

Trends in fractures in patients with spondyloarthritis: a nationwide population-based study (TREND-EspA study).

Our aim was to analyze trends in fracture rates in SpA patients over an extended time period. Only an increase of axial fractures, more specifically vertebral fractures, is observed in SpA. PURPOSE: To analyze fracture incidence and trend in patients with spondyloarthritis (SpA) over an extended time period. METHODS: Retrospective observational population-based study with matched cohorts. Data from the Minimum Basic Data Set (MBDS) of Spain were reviewed. All SpA patient hospitalizations reported from 1999 to 2015 (SpA cohort) were analyzed. A control cohort (non-SpA cohort) matched by age, sex, region, and year of hospitalization was recruited. The age and sex-adjusted crude incidence rate was calculated for any fractures (axial and peripheral). Generalized linear models (GLM) were used for trend analysis. Association between fracture type and SpA (and its subtypes) was assessed using unconditional logistic regression models. RESULTS: In the SpA cohort, the age and sex-adjusted rates per 100,000 inhabitants/year of total fracture and different types of fracture were 45.72 any fractures, 17.64 axial, and 28.02 peripheral; 29.42 osteoporotic (12.67 vertebra, 12.29 hip, 1.50 pelvis, 1.82 humerus and 2.09 radius). In the non-SpA cohort, they were 65.79 any, 12.08 axial, 51.52 peripheral; 31.17 osteoporotic (4.94 vertebra, 16.15 hip, 2.29 pelvis, 3.64 humerus, 5.38 radius). Between 1999 and 2015, the trend in incidence rate for total fracture and different types of fracture increased similarly for both cohorts. In the SpA cohort, an increase of axial fractures was found (AOR 1.444; 95%CI 1.297-1.609), and specifically of vertebral fractures (AOR 2.440; 95%CI 2.097-2.839). Other types of fractures did not increase. CONCLUSIONS: Only an increase of axial fractures, more specifically vertebral fractures, is observed in SpA. Trend in incidence is similar in both cohorts.

[The Spanish National Hip Fractures Registry (RNFC) and the Minimum Basic Data Set (CMBD) are useful for research on hip fractures: comparison of two registries.] / El Registro Nacional de Fracturas de Cadera (RNFC) y el Conjunto Mínimo Básico de Datos son útiles para investigar sobre fracturas de cadera: comparación de ambos registros.

OBJECTIVE: National hip fracture registries have been established in several countries and recent publications show that the care process has been audited inspecting the representativeness according to quality standards. The aim of this study was to analyse if the Spanish National Hip Fracture Registry (RNFC) represents the Spanish population aged 75 and older admitted for hip fractures, and to compare its results regarding the care process with the national average, according to the National Inpatient register (Minimum Basic Dataset, CMBD). METHODS: The 2017-2018 National Minimum Basic Dataset (Conjunto Mínimo Básico de Datos, CMBD) was used as reference. For analysis, we included 83,110 cases from the CMBD and 21,130 from the RNFC. Eight common variables of both registries were selected for comparison. RESULTS: No significant differences were observed in the patient-related common variables (age, sex, type of fracture and fracture side), but statistically significant differences were found in the variables describing the care process (proportion of patients operated, deceased, surgical procedures and postoperative length of stay). CONCLUSIONS: The RNFC, designed as a convenience sample, is also representative of the population of patients aged 75 and older treated for hip fractures in Spain. However, there is a participation bias related to the professionals and the hospitals interested in voluntarily participating in a quality improvement program, which would explain the better results observed in the care process, compared to the national average as collected by the CMBD.

OBJETIVO: Los registros nacionales de fracturas de cadera se han establecido en varios países y publicaciones recientes muestran que el proceso de atención ha sido auditado para explorar su representatividad de acuerdo a estándares de calidad. El objetivo de este trabajo fue analizar si el Registro Nacional de Fracturas de Cadera (RNFC) es representativo de la población española de 75 o más años de edad ingresada por fractura de cadera, y comparar los resultados acerca del proceso asistencial con la media nacional según el Conjunto Mínimo Básico de Datos (CMBD). METODOS: Se empleó el CMBD de los años 2017-2018 como referencia. Para el análisis se incluyeron 83.110 casos del CMBD y 21.130 del RNFC. Se seleccionaron ocho variables comunes a ambos registros para ser comparadas. RESULTADOS: No se observaron diferencias significativas en las variables comunes paciente-dependientes (edad, sexo, tipo y lado de fractura), pero se hallaron diferencias significativas en las variables que describían el proceso asistencial (proporción de pacientes intervenidos, fallecidos, tipos de procedimiento quirúrgico y estancia postoperatoria). CONCLUSIONES: El RNFC, diseñado como muestra de conveniencia, es también representativa de la población de pacientes de 75 y más años, atendida por fractura de cadera en España. Sin embargo, existe un sesgo de participación relacionado con los profesionales y los hospitales interesados en participar voluntariamente en un programa voluntario de mejora de calidad que podría explicar los mejores resultados observados en el proceso asistencial, comparado con la media nacional según se recoge por el CMBD.

Trends in amyloidosis in spondyloarthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999-2015)-TREND-EspA study.

OBJECTIVE: To assess the incidence of amyloidosis and trends therein in patients with spondyloarthritis (SpA) over a long period (17 years). METHODS: An observational retrospective population-based matched cohort study was conducted. All the admissions of patients with SpA, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis associated with inflammatory bowel disease (SpA-IBD) and reactive arthritis (ReA), reported between 1999 and 2015, were analysed and a control group matched by age, sex and year of admission was selected. Incidence rates for amyloidosis were calculated. Generalised linear models were used for trend analysis and unconditional logistic regression for calculating crude and adjusted ORs (AOR) to assess the association between amyloidosis and SpA. RESULTS: The study database contained data on 107 140 admissions in each group. Between 1999 and 2015, 792 patients in the SpA cohort (0.7% of all admissions) had a diagnosis of amyloidosis versus 68 in the non-SpA cohort (0.1%) (p<0.001). From 1999 to 2015, incidence rates of amyloidosis tended to decrease in the SpA cohort (-4.63%/year overall), while they increased in the Non-SpA cohort (+10.25%/year overall). We found strong associations of amyloidosis with all SpAs (AOR 10.4; 95% CI 8.2 to 13.3) and with each type studied (AORs 10.05 (7.84 to 12. 88) for AS, 9.5 (7.3 to 12.4) for PsA, 22.9 (16.6 to 31.7) for SpA-IBD and 10.1 (6.1 to 16.7) for ReA). CONCLUSIONS: Incidence of amyloidosis among patients with SpA has strongly decreased in Spain. Amyloidosis is most strongly associated with SpA-IBD while the strength of association with PsA and ReA is similar to that with AS.

Risk of acute myocardial infarction among new users of chondroitin sulfate: A nested case-control study.

OBJECTIVE: To test the hypothesis that the use of chondroitin sulfate (CS) or glucosamine reduces the risk of acute myocardial infarction (AMI). DESIGN: Case-control study nested in a primary cohort of patients aged 40 to 99 years, using the database BIFAP during the 2002-2015 study period. From this cohort, we identified incident cases of AMI and randomly selected five controls per case, matched by exact age, gender, and index date. Adjusted odds ratios (AOR) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of CS or glucosamine were considered. RESULTS: A total of 23,585 incident cases of AMI and 117,405 controls were included. Of them, 89 cases (0.38%) and 757 controls (0.64%) were current users of CS at index date, yielding an AOR of 0.57 (95%CI: 0.46-0.72). The reduced risk among current users was observed in both short-term (<365 days, AOR = 0.58; 95%CI: 0.45-0.75) and long-term users (>364 days AOR = 0.56; 95%CI:0.36-0.87), in both sexes (men, AOR = 0.52; 95%CI:0.38-0.70; women, AOR = 0.65; 95%CI:0.46-0.91), in individuals over or under 70 years of age (AOR = 0.54; 95%CI:0.38-0.77, and AOR = 0.61; 95%CI:0.45-0.82, respectively) and in individuals at intermediate (AOR = 0.65; 95%CI:0.48-0.91) and high cardiovascular risk (AOR = 0.48; 95%CI:0.27-0.83), but not in those at low risk (AOR = 1.11; 95%CI:0.48-2.56). In contrast, the current use of glucosamine was not associated with either increased or decreased risk of AMI (AOR = 0.86; 95%CI:0.66-1.08). CONCLUSIONS: Our results support a cardioprotective effect of CS, while glucosamine seems to be neutral. The protection was remarkable among subgroups at high cardiovascular risk.

[Democracy and Covid-19 mortality in Europe.] / Democracia y mortalidad por Covid-19 en Europa.

OBJECTIVE: In Europe there is a great variability in mortality by Covid-19 among different countries. While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants. It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability. The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries. METHODS: This is a retrospective, multinational, ecological study based on the exploitation of the database provided by the European Centre for Disease Prevention and Control which collects daily information worldwide on new cases and deaths. The accumulated mortality of Covid-19 in European countries (with more than 100 deaths on 01/05/2020) was calculated up to 29/05/2020. Political variables were compiled from different sources in the countries included in the study. The variables analysed were: the democracy index and the different factors included in it, the country's political system and the country's corruption index. On the other hand, specific political measures implemented in the different countries were collected, such as the number of days elapsed from the notification of the first infected person to 100 infected persons, to lockdown, to the closure of schools or the cancelation of meetings. The number of people infected up to the date of lockdown was also registered. For the statistical analysis of the association between the dependent variable (mortality) and the factors studied, correlation index were calculated, and the association was studied through univariate and multivariate linear regression models. RESULTS: At May 1 2020, 27 European countries had at least 100 deaths. The mean mortality was 19.83 cases/100,000 inhabitants (SD 22.4) and a median of 7.95. Mortality varied from a minimum of 1.49 cases/100,000 population in Ukraine to 82.19 cases/100,000 population in Belgium. About factors analyzed both the democracy index (as well as the factors included in it), the political system (full democracy vs. no) and the corruption index were statistically associated with mortality. Also, the time until the implementation of the political measures was associated with mortality. CONCLUSIONS: In Europe, there is a west to east (from highest to lowest) gradient in the mortality of Covid-19. Some of the observed mortality variability can be explained by political factors.

OBJETIVO: En Europa hay una gran variabilidad en la mortalidad por Covid-19 entre los diferentes países. Mientras que algunos países, como Grecia, Bielorrusia o Ucrania, la mortalidad no alcanza los 5 casos por cada 100.000 habitantes actualmente, otros países como Bélgica, España o Reino Unido sobrepasan marcadamente los 50 casos por cada 100.000 habitantes. En general, se especula en que el motivo de esta variabilidad es multifactorial (entre ellos, motivos de índole política), pero existen escasos estudios que asocien factores relacionados con esta variabilidad. El objetivo de este trabajo fue analizar los factores/marcadores de riesgo de índole político que pudieran explicar la variabilidad en la mortalidad por Covid-19 entre los diferentes países europeos. METODOS: Estudio ecológico, observacional retrospectivo, de ámbito multinacional, basado en la explotación de la base de datos proporcionada por el European Centre for Disease Prevention and Control que recoge la información diaria a nivel mundial de los nuevos casos y fallecidos. Se calculó la mortalidad acumulada de Covid-19 en países europeos (con más de 100 fallecidos a fecha de 1 de mayo de 2020), hasta el 29 de mayo de 2020. Se recogieron variables de carácter político de los países incluidos en el estudio de diferentes fuentes. Las variables analizadas fueron: índice de democracia y los diferentes factores incluidos en él, sistema político del país e índice de corrupción del país. Por otra parte, se recogieron medidas políticas específicas implementadas en los distintos países, como los días transcurridos desde la notificación del primer infectado hasta llegar a los 100 infectados, así como los días transcurridos hasta el confinamiento, hasta el cierre de colegios o hasta el cese de reuniones. También se recogió el número de infectados hasta la fecha de confinamiento. Para el análisis estadístico de la asociación entre la variable dependiente (mortalidad) y los factores estudiados se calcularon índices de correlación, y la asociación se estudió a través de modelos de regresión lineal univariante y multivariante. RESULTADOS: A fecha de 1 de mayo de 2020, 27 países europeos contaban con al menos 100 fallecidos. La media de la mortalidad fue de 19,83 casos por cada 100.000 hab. (DE 22,4) y una mediana de 7,95. La mortalidad varió desde un mínimo de 1,49 casos por cada 100.000 hab. en Ucrania hasta 82,19 casos por cada 100.000 hab. en Bélgica. De los factores analizados, tanto el índice de democracia (como los factores incluidos en él) como el sistema político (democracia plena frente a no) y el índice de corrupción se asociaron estadísticamente con la mortalidad. También, el tiempo transcurrido hasta la implantación de las medidas políticas se asoció con mortalidad. CONCLUSIONES: En Europa, existe un degradado de oeste a este (de mayor a menor) en la mortalidad por Covid-19. Parte de la variabilidad de la mortalidad observada puede explicarse por factores de índole política.

Orthopedic Surgery in Rheumatoid Arthritis: Results from the Spanish National Registry of Hospitalized Patients over 17 Years.

OBJECTIVE: To analyze the trend of orthopedic surgery (OS) rates on patients with rheumatoid arthritis (RA). METHODS: Retrospective observational study based on information provided by the Spanish National System of Hospital Data Surveillance. All hospitalizations of patients with RA for orthopedic surgery [total hip arthroplasty (THA), total knee arthroplasty (TKA), arthrodesis, and upper limb arthroplasty (ULA)] during 1999-2015 were analyzed. The age-adjusted rate was calculated. Generalized linear models were used for trend analysis. RESULTS: There were 21,088 OS in patients over 20 years of age (77.9% women). OS rate adjusted by age was 754.63/100,000 RA patients/year (women 707.4, men 861.1). Neither an increasing nor a decreasing trend was noted for the total OS. However, trend and age interacted, so in the age ranges 20-40 years and 40-60 years, an annual reduction of 2.69% and 2.97%, respectively, was noted. In the age ranges over 80 years and 60-80 years, we noted an annual increase of 5.40% and 1.09%, respectively. The average age at time of OS increased 5.5 years during the period analyzed. For specific surgeries, a global annual reduction was noted in rates for arthrodesis. In THA, there was an annual reduction in patients under 80 years. In TKA and ULA, there was an annual reduction in patients under 60 years. CONCLUSION: Although the overall OS rate has not changed, there is a decrease in the rate of arthrodesis at all ages, THA in patients under 80 years of age, as well as TKA and ULA in patients under 60 years of age.

Democracia y mortalidad por COVID-19 en Europa / Democracy and Covid-19 mortality in Europe

OBJETIVO: En Europa hay una gran variabilidad en la mortalidad por Covid-19 entre los diferentes países. Mientras que algunos países, como Grecia, Bielorrusia o Ucrania, la mortalidad no alcanza los 5 casos por cada 100.000 habitantes actualmente, otros países como Bélgica, España o Reino Unido sobrepasan marcadamente los 50 casos por cada 100.000 habitantes. En general, se especula en que el motivo de esta variabilidad es multifactorial (entre ellos, motivos de índole política), pero existen escasos estudios que asocien factores relacionados con esta variabilidad. El objetivo de este trabajo fue analizar los factores/marcadores de riesgo de índole político que pudieran explicar la variabilidad en la mortalidad por Covid-19 entre los diferentes países europeos. MÉTODOS: Estudio ecológico, observacional retrospectivo, de ámbito multinacional, basado en la explotación de la base de datos proporcionada por el European Centre for Disease Prevention and Control que recoge la información diaria a nivel mundial de los nuevos casos y fallecidos. Se calculó la mortalidad acumulada de Covid-19 en países europeos (con más de 100 fallecidos a fecha de 1 de mayo de 2020), hasta el 29 de mayo de 2020. Se recogieron variables de carácter político de los países incluidos en el estudio de diferentes fuentes. Las variables analizadas fueron: índice de democracia y los diferentes factores incluidos en él, sistema político del país e índice de corrupción del país. Por otra parte, se recogieron medidas políticas específicas implementadas en los distintos países, como los días transcurridos desde la notificación del primer infectado hasta llegar a los 100 infectados, así como los días transcurridos hasta el confinamiento, hasta el cierre de colegios o hasta el cese de reuniones. También se recogió el número de infectados hasta la fecha de confinamiento. Para el análisis estadístico de la asociación entre la variable dependiente (mortalidad) y los factores estudiados se calcularon índices de correlación, y la asociación se estudió a través de modelos de regresión lineal univariante y multivariante. RESULTADOS: A fecha de 1 de mayo de 2020, 27 países europeos contaban con al menos 100 fallecidos. La media de la mortalidad fue de 19,83 casos por cada 100.000 hab. (DE 22,4) y una mediana de 7,95. La mortalidad varió desde un mínimo de 1,49 casos por cada 100.000 hab. en Ucrania hasta 82,19 casos por cada 100.000 hab. en Bélgica. De los factores analizados, tanto el índice de democracia (como los factores incluidos en él) como el sistema político (democracia plena frente a no) y el índice de corrupción se asociaron estadísticamente con la mortalidad. También, el tiempo transcurrido hasta la implantación de las medidas políticas se asoció con mortalidad. CONCLUSIONES: En Europa, existe un degradado de oeste a este (de mayor a menor) en la mortalidad por Covid-19. Parte de la variabilidad de la mortalidad observada puede explicarse por factores de índole política

OBJECTIVE: In Europe there is a great variability in mortality by Covid-19 among different countries. While some countries, such as Greece, Belarus or Ukraine, have a mortality rate of less than 5 cases/100,000 inhabitants, other countries such as Belgium, Spain or the United Kingdom have a mortality rate of well over 50 cases/100,000 inhabitants. It is generally considered that the reason for this variability is multifactorial (including political reasons), but there are few studies that associate factors related to this variability. The objective of this work was to analyse political risk factors/markers that could explain the variability in mortality due to Covid-19 among different European countries. METHODS: This is a retrospective, multinational, ecological study based on the exploitation of the database provided by the European Centre for Disease Prevention and Control which collects daily information worldwide on new cases and deaths. The accumulated mortality of Covid-19 in European countries (with more than 100 deaths on 01/05/2020) was calculated up to 29/05/2020. Political variables were compiled from different sources in the countries included in the study. The variables analysed were: the democracy index and the different factors included in it, the country's political system and the country's corruption index. On the other hand, specific political measures implemented in the different countries were collected, such as the number of days elapsed from the notification of the first infected person to 100 infected persons, to lockdown, to the closure of schools or the cancelation of meetings. The number of people infected up to the date of lockdown was also registered. For the statistical analysis of the association between the dependent variable (mortality) and the factors studied, correlation index were calculated, and the association was studied through univariate and multivariate linear regression models. RESULTS: At May 1 2020, 27 European countries had at least 100 deaths. The mean mortality was 19.83 cases/100,000 inhabitants (SD 22.4) and a median of 7.95. Mortality varied from a minimum of 1.49 cases/100,000 population in Ukraine to 82.19 cases/100,000 population in Belgium. About factors analyzed both the democracy index (as well as the factors included in it), the political system (full democracy vs. no) and the corruption index were statistically associated with mortality. Also, the time until the implementation of the political measures was associated with mortality. CONCLUSIONS: In Europe, there is a west to east (from highest to lowest) gradient in the mortality of Covid-19. Some of the observed mortality variability can be explained by political factors

Risk of Acute Myocardial Infarction Among New Users of Allopurinol According to Serum Urate Level: A Nested Case-Control Study.

OBJECTIVES: To test the hypothesis that allopurinol reduces the risk of acute myocardial infarction (AMI) in hyperuricemic patients and to assess whether the effect is dependent on dose, duration and serum uric acid (SUA) level attained after treatment. METHODS: Nested case-control study over the period 2002-2015. From a cohort of patients aged 40-99 years old, we identified incident AMI cases and randomly selected five controls per case, matched for exact age, sex and index date. Adjusted odds ratios (AOR) and 95% CI were computed through unconditional logistic regression. Only new users of allopurinol were considered. RESULTS: A total of 4697 AMI cases and 18,919 controls were included. Allopurinol use was associated with a reduced risk of AMI mainly driven by duration of treatment (AOR ≥180 days = 0.71; 95% CI: 0.60-0.84). Among long-term users (≥180 days), the reduced risk was only observed when the SUA level attained was below 7 mg/dL (AOR<6 mg/dL = 0.64; 95% CI: 0.49-0.82; AOR6-7mg/dL = 0.64; 95%CI:0.48-0.84); AOR>7mg/dL = 1.04; 95% CI: 0.75-1.46; p for trend = 0.001). A dose-effect was observed but faded out once adjusted for the SUA level attained. The reduced risk of AMI occurred in both patients with gout and patients with asymptomatic hyperuricemia. CONCLUSIONS: The results confirm a cardioprotective effect of allopurinol which is strongly dependent on duration and SUA level attained after treatment.

East-west gradient in hip fracture incidence in Spain: how much can we explain by following the pattern of risk factors?

Our objective was to analyze the incidence and trend of hip fracture in Spain and its distribution by Autonomous Community (AC). In Spain, the age-adjusted incidence rate of hip fracture is decreasing. There is great variability in the incidence and tendency of hip fracture among the different ACs. Genetic, demographic, and climatic factors and cohort effect factors of the civil war explain 96% of this variability. INTRODUCTION: In Spain, there is great variability between the different Autonomous Communities (ACs) in the incidence of hip fracture. The objectives of our study are (1) to estimate the incidence rate and trend of hospital admissions for hip fracture in Spain and by ACs and (2) to analyze risk factors/markers that could explain the variability in the incidence and trend between different ACs. METHOD: This work includes 2 studies (TREND-HIP and VAR-HIP). TREND-HIP: retrospective, national, observational study based on the administrative database of the National Health System that includes a Minimum Basic Data Set (MBDS) of hospital admissions. VAR-HIP: ecological study based on the analysis of the results obtained in TREND-HIP study, with different risk factors/markers obtained from different sources. RESULTS: In the 17 years included in the analysis, there were 744,848 patients diagnosed with hip fracture. The global age-adjusted rate of hip fracture at the national level was 315.38/100,000 person*year (95% CI 312.36-317.45); by AC, the rate varied from 213.97 in the Canary Islands to 363.13 in the Valencia and Cataluña communities. We observe an east-west gradient in Spain. The trend for both sexes was - 0.67% (95% CI 0.9990-0.9957) (p < 0.001). In the analysis of risk factors/markers that explain this distribution, we found significant correlations with genetic factors, demographics, climatic factors and the time a region was on the Republican side of the civil war. The linear regression model that includes the factors that show significant correlation explains 96% of the variability observed. CONCLUSION: In Spain, the age-adjusted incidence rate for hip fracture is decreasing. There is a great variability in the incidence and tendency of hip fracture among the different ACs. Genetic, demographic, climatic factors and the cohort effect of the civil war explain 96% of this variability.

Mortality after osteoporotic hip fracture: incidence, trends, and associated factors.

BACKGROUND: It is known that mortality after hip fracture increases compared to the general population; the trend in mortality is a controversial issue. The objective of this study is to examine incidence, trends, and factors associated with mortality in patients with osteoporotic hip fractures. METHODS: This is a retrospective cohort study that uses the Registry for Hospital Discharges of the National Health System of our hospital. Patients older than 45 having an osteoporotic hip fracture between 1999 and 2015 were identified. Demographic data and comorbidities were obtained. A survival analysis was performed (Cox regression and Kaplan-Meier). Incidence rate, standardized death rate (SDR), trend (Poisson regression), and risk (hazard ratio) were calculated. RESULTS: During 1999-2015, in our hospital, there were a total of 3992 patients admitted due to osteoporotic hip fracture. Out of these 3992 patients, 3109 patients (77.9%) were women with an average age of 84.47 years (SD 8.45) and 803 (22.1%) were men with an average age of 81.64 years (SD 10.08). The cumulative incidence of mortality was 69.38%. The cumulative mortality rate for 12 months was 33%. The annual mortality was 144.9/1000 patients/year. The 1-year mortality rate increased significantly by 2% per year (IRR 1.020, CI95% 1.008-1.033). The median overall survival was 886 days (CI95% 836-951). The probability of mortality density for a period of 10 years following a hip fracture was 16% for women and 25% for men (first 90 days). The SDR was 8.3 (CI95% 7.98-8.59). Variables that showed statistically significant association with mortality were aged over 75, masculine, institutionalization, mild to severe liver disease, chronic kidney disease, COPD, dementia, heart failure, diabetes, the Charlson Index > 2 , presence of vision disorders and hearing impairment, incontinence, and Downton scale. CONCLUSIONS: For the last 17 years, an increase of mortality for patients with hip fracture and a higher mortality rate in men than in women were observed. Institutionalization combined with comorbidities is associated with a higher mortality.

Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología / A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics

Objetivo: El paradigma actual en el tratamiento de la artritis reumatoide (AR) contempla el diagnóstico temprano y el uso precoz de fármacos modificadores de enfermedad (FAME) para alcanzar la remisión o baja actividad inflamatoria, lo cual, se conoce como «treat to target» (T2T). El objetivo del trabajo es desarrollar un indicador compuesto (IC) para evaluar la calidad asistencial en el manejo de los pacientes con AR atendiendo a la estrategia T2T y a otras recomendaciones generales para la atención de estos pacientes. Material y método: La construcción del IC siguió las fases: 1) selección de los criterios de calidad mediante un juicio de expertos; 2) priorización de los criterios, a partir de un Delphi con 20 expertos; 3) diseño de los indicadores de calidad, y 4) cálculo del IC ponderado. La fuente de información para el cálculo del IC son las historias clínicas de los pacientes con AR. Resultados: De los 37 criterios seleccionados, 12 necesitaron una segunda ronda Delphi. Se priorizaron 31 criterios, los cuales presentaron una mediana en relevancia y factibilidad, en las rondas Delphi, mayor o igual a 7,5, con un rango intercuartílico inferior a 3,5, y un grado de acuerdo (puntuación mayor o igual a 8) igual o superior al 80%. Conclusiones: El IC construido, consensuado y ponderado, permite evaluar la calidad asistencial de los pacientes con AR, en las Unidades de Reumatología de hospitales españoles, ofreciendo una medida resumen válida y fácilmente interpretable

Objective: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. Material and method: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. Results: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. Conclusions: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure

A composite indicator to assess the quality of care in the management of patients with rheumatoid arthritis in outpatient rheumatology clinics. / Indicador compuesto para evaluar la calidad asistencial en el manejo de los pacientes con artritis reumatoide en las consultas externas de Reumatología.

OBJECTIVE: The current guidelines in the treatment of rheumatoid arthritis (RA) include the early diagnosis and early use of disease modifying drugs to achieve remission or low disease activity level, known as "Treat to Target" (T2T). The objective of this study is to develop a composite indicator (CI) to evaluate the quality of care in the management of patients with RA, according to the T2T strategy and other general recommendations concerning the management of these patients. MATERIAL AND METHOD: The phases of the construction of the CI were: 1) selection of quality criteria through expert judgment; 2) prioritization of the criteria, according to relevance and feasibility, applying the Delphi methodology (two rounds) involving 20 experts; 3) design of quality indicators; and 4) calculation of the weighted CI, using the mean value in relevance and feasibility granted by the experts. The source of information for the calculation of the CI are the medical records of patients with RA. RESULTS: Twelve criteria out of 37 required a second Delphi round. Thirty-one criteria were prioritized. These criteria presented a median in relevance and feasibility greater than or equal to 7.5, with an interquartile range of less than 3.5, and a level of agreement (score greater than or equal to 8) greater than or equal to 80%. CONCLUSIONS: The constructed CI allows us to evaluate the quality of care of patients with RA following the T2T strategy in the rheumatology units of Spanish hospitals, offering a valid and easily interpretable summary measure.

Trends in hip fracture in patients with rheumatoid arthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999-2015). TREND-AR study.

PURPOSE: To analyse trends in hip fracture (HF) rates in patients with rheumatoid arthritis (RA) over an extended time period (17 years). METHODS: This observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalisations of patients with RA and HF that were reported from 1999 to 2015 were analysed. Codes were selected using the Ninth International Classification of Diseases, Clinical Modification: ICD-9-CM: RA 714.0 to 714.9 and HF 820.0 to 820.3. The crude and age-adjusted incidence rate of HF was calculated by age and sex strata over the last 17 years. General lineal models were used to analyse trends. RESULTS: Between 1999 and 2015, 6656 HFs occurred in patients with RA of all ages (84.25% women, mean age 77.5 and 15.75% men, mean age 76.37). The age-adjusted osteoporotic HF rate was 221.85/100 000 RA persons/ year (women 227.97; men 179.06). The HF incidence rate increased yearly by 3.1% (95% CI 2.1 to 4.0) during the 1999-2015 period (p<0.001) and was more pronounced in men (3.5% (95% CI 2.1 to 4.9)) than in women (3.1% (95% CI 2.3 to 4.1)). The female to male ratio decreased from 1.54 in 1999 to 1.14 in 2015. The average length of hospital stays (ALHS) decreased (p<0.001) from 16.76 days (SD 15.3) in 1999 to 10.78 days (SD 7.72) in 2015. Age at the time of hospitalisation increased (p<0.001) from 75.3 years (SD 9.33) in 1999 to 79.92 years (SD 9.47) in 2015. There was a total of 326 (4.9%) deaths during admission, 247 (4.4%) in women and 79 (7.5%) in men (p<0.001). CONCLUSION: In Spain, despite the advances that have taken place in controlling disease activity and in treating osteoporosis, the incidence rate of HF increased in both male and female patients with RA.

High Reproducibility of an Automated Measurement of Mobility for Patients with Axial Spondyloarthritis.

OBJECTIVE: Conventional measures of spinal mobility used in the assessment of patients with axial spondyloarthritis (axSpA), such as the Bath Ankylosing Spondylitis Metrology Index and its components, are subject to interobserver variability. The University of Córdoba Ankylosing Spondylitis Metrology Index (UCOASMI) is a validated composite index based on a motion video-capture system, UCOTrack. Our objective was to assess its reproducibility in clinical practice settings. METHODS: We carried out an observational study of repeated measures in 3 centers. Video-capture systems were installed and adapted to clinical rooms. Patients with axSpA and stable disease were selected by consecutive stratified sampling [disease duration, sex, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)]. Intraobserver reliability of the UCOASMI and of conventional measures was tested 3-5 days apart. For interobserver reliability, 3 patients from each center were evaluated in the other centers, within 3-7 days. The intraclass correlation coefficients (ICC) were calculated. RESULTS: Thirty patients were included (73% men, mean age 53 yrs, mean BASDAI 3.0). Interobserver and intraobserver ICC of the UCOASMI was 0.98. Conventional measurements showed lower but adequate reproducibility as well, except for interobserver reliability of lateral flexion (0.41), cervical rotation (0.61), and Schöber test (0.07), and intraobserver reliability of tragus-to-wall distance (0.30). CONCLUSION: Reproducibility of the UCOASMI seems very high, and apparently more reliable than conventional measures of mobility.

Weather conditions and their effect on seasonality of incident osteoporotic hip fracture.

Our aim was to analyze the seasonality and the effect of weather conditions on the incidence of osteoporotic hip fracture in a Southern European region. INTRODUCTION: The objective of this work is to evaluate seasonality and the effect of weather conditions on the incidence of osteoporotic hip fracture in a Southern European region. METHODS: This retrospective cohort study included all patients admitted to Alcorcón Foundation University Hospital with a diagnosis of osteoporotic hip fracture between the years 1999 and 2015. In a time series analysis, we examined the association between hip fracture incidence and different weather conditions and seasonality using general additive models (with Poisson distribution). The incidence rate ratio (IRR) crude and adjusted by season was estimated for all parameters. Hip incidence was further analyzed by sex and age (below or over 75) subgroups. RESULTS: Four thousand two hundred seventy-one patients with an osteoporotic hip fracture were included (79% females, mean age 83.8). Season fracture rate was significantly higher in fall and winter (67.06 and 64.41 fractures/season) compared to summer and spring (59.71 and 60.06; p < 0,001). Hip fracture incidence was 15% greater in autumn and winter than in spring and summer. Fog [IRR 1.15 (95% CI: 1.003-1.33)], atmospheric pressure (per 100 mb) [IRR 1.05 (95% CI: 1.004-1.114)], and frost [IRR 1.15 (95% CI: 1.03-1.30)] were significantly associated with increased hip fracture. Haze [IRR 1.10 (95% CI: 0.99-1.23)] showed a trend without statistical significance. Daily average temperature (per 5 °C) [IRR 0.98 (95% CI: 0.957-0.996)], rain (per 10 ml) [IRR 0.99 (95% CI: 0.981-1.0)], wind speed [IRR = 0.952, (95% CI: 0.907-0.998)], and daily ultraviolet radiation (per 100 joules) [IRR 0.998 (95% CI: 0.996-1.0)] were negatively associated with fracture. After adjusting by season and trend, all these associations disappear. CONCLUSIONS: In this Southern region, hip fracture incidence exhibits a seasonal pattern different from those communicated in Northern regions. There is short-term association with different weather conditions that partly explain this seasonal pattern.