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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.
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COVID-19 , Miocarditis , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Miocarditis/diagnóstico , Miocarditis/etiología , Miocarditis/terapia , Vacunación , Vacunas de ARNm , Prueba de COVID-19RESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.
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Non-inferiority studies are increasingly more common for introducing new medicines in the market. Despite being situations where the use of this study design is justified, there is not a common analytical approach on how to conduct them. Pursuing a rigorous methodology, both in the study conduction and in its disseminations, is critical to ensure robust results to enable regulatory agencies and clinicians to reach valid conclusions and decisions which ultimately will benefit clinical practice. Most of the published reviews focus on the efficacy outcomes of non-inferiority clinical trials. We are unaware of other reviews that goes beyond and includes specific aspects for non-interventional designs and for studies focused on safety. Moreover, this review provides a simple and practical perspective with a minimum mathematical content on this complex type of studies.
Los estudios de no inferioridad son cada vez más frecuentes para introducir nuevos medicamentos en el mercado. Aunque existen situaciones en las que su uso está justificado, no existe un enfoque analítico único y conservador. Para arrojar resultados fiables y de calidad, deben seguir una estricta metodología, tanto en la ejecución como en la difusión de los resultados, la cual permita, tanto a las agencias reguladoras como a los clínicos, establecer conclusiones válidas y decisiones que repercutan en beneficio de la práctica clínica. La mayor parte de las revisiones publicadas se centran en los ensayos clínicos de no inferioridad de eficacia. En esta revisión se contemplan, además, los diseños observacionales y los aspectos específicos de los estudios de seguridad. Todo ello desde un punto de vista práctico y sencillo, con un contenido matemático mínimo.
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Proyectos de Investigación , Humanos , EspañaRESUMEN
BACKGROUND: Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain. METHODS: In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis. RESULTS: Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79-1.76] for exposed (1.25 [0.77-2.04] for bi- and 1.15 [0.76-1.76] for quadri-valent vaccines) and 1.26 [0.74-2.14] for post-exposed periods. HR was 1.50 [0.87-2.59] for the 1st dose, 1.13 [0.66-1.91] for the 2nd and 1.11 [0.71-1.72] for the 3rd one. When the diagnosis date was moved back, the risk was 1.14 [0.76-1.70] for exposed period, being 1.80 [0.86-3.76] and 1.40 [0.74-2.66] after 1st dose of bi- and quadri-valent, respectively. CONCLUSIONS: We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1st HPV vaccination dose than after subsequent doses, a dose-effect was not confirmed. Results remained similar after applying a lag time.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Tiroiditis , Neoplasias del Cuello Uterino , Estudios de Cohortes , Femenino , Humanos , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Estudios Retrospectivos , Tiroiditis/inducido químicamente , Tiroiditis/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Vacunación/efectos adversosRESUMEN
OBJECTIVES: We aimed to develop and validate a fracture risk algorithm for the automatic identification of subjects at high risk of imminent and long-term fracture risk. RESEARCH, DESIGN, AND METHODS: A cohort of subjects aged 50-85, between 2007 and 2017, was extracted from the Catalan information system for the development of research in primary care database (SIDIAP). Participants were followed until the earliest of death, transfer out, fracture, or 12/31/2017. Potential risk factors were obtained based on the existing literature. Cox regression was used to model 1 and 5-year risk of hip and major fracture. The original cohort was randomly split in 80:20 for development and internal validation purposes respectively. External validation was explored in a cohort extracted from the Spanish database for pharmaco-epidemiological research in primary care. RESULTS: A total of 1.76 million people were included from SIDIAP (50.7 % women with mean age of 65.4 years). Hip and major fracture incidence rates were 3.57 [95%CI 3.53 to 3.60] and 11.61 [95%CI 11.54 to 11.68] per 1000 person-years, respectively. The derived model included 19 risk factors. Internal validity showed good results on calibration and discrimination. The 1-year C-statistic for hip and major fracture were 0.851 (95%CI 0.853 to 0.864), and 0.717 (95%CI 0.742 to 0.749) respectively. The 5-year C-statistic for hip and major fracture were 0.849 (95%CI 0.847 to 0.852) and 0.724 (95%CI 0.721 to 0.727) respectively. External validation showed good performance for hip and major fracture risk prediction. CONCLUSIONS: We have developed and validated a clinical prediction tool for 1- and 5-year hip and major osteoporotic fracture risks using electronic primary care data. The proposed algorithm can be automatically estimated at the population level using the available primary care records. Future work is needed on the cost-effectiveness of its use for population-based screening and targeted prevention of osteoporotic fractures.
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Fracturas de Cadera , Fracturas Osteoporóticas , Anciano , Algoritmos , Registros Electrónicos de Salud , Femenino , Fracturas de Cadera/etiología , Humanos , Masculino , Fracturas Osteoporóticas/epidemiología , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
BACKGROUND: Liver injury is an important identified risk for agomelatine and several measures were put in place to prevent and minimize such risk. The study aims to assess the impact of four interventions on the incidence of agomelatine use, particularly among patients aged ≥75 in Spain between 2011 and 2018. METHODS: Quasi-experimental interrupted time-series analysis to examine data from a nationwide electronic healthcare record database (BIFAP). Quarterly cumulative incidence of agomelatine use per 100 000 patients was calculated and the impact of four regulatory interventions was quantified. RESULTS: The incidence of agomelatine use decreased by 85% and 87% from first quarter 2011 to last quarter 2018 in patients below and above 75 years old, respectively. Regulatory actions taken were not associated with an immediate and significant falling level of use or slope. The incidence was less than expected 6 months after the first and third intervention for patients below and above 75 years old, and more than expected after the second and fourth intervention for both populations, though these analyses were underpowered to observe significant results. The downward trend became less pronounced, reaching a residual level of use, which remained stable in the last segment of the study period. CONCLUSION: New users of agomelatine decreased throughout the study period, starting before interventions took place. The effect of specific interventions might be masked by the progressive decrease tendency, constant over the study period. The effects of external factors that might overlap, unintended consequences, and issues concerning statistical modeling in situations where rates are already falling, should be considered when interpreting the results.
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Acetamidas , Atención a la Salud , Acetamidas/uso terapéutico , Anciano , Electrónica , Humanos , España/epidemiologíaRESUMEN
BACKGROUND: Studies of the association of Guillain-Barré Syndrome (GBS) with papillomavirus vaccination (HPVv; scheduled from 2007) have provided contradicting results, probably due to the low frequency of this disease. We aimed at estimating that risk relative to non-vaccination among girls, by using the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP). METHODS: A cohort study of girls aged 9-18 years during 2007-2016 free of GBS or HPVv was selected and followed up to GBS diagnosis. Follow-up time was divided by time-varying HPVv exposure and confounders. Crude Incidence rates (IR per 1,000,000 person-years (py)) and adjusted Hazard Ratios (HR) of GBS were estimated anytime after vaccination compared to non-exposed periods. HRs were also estimated for the first 90 days after HPVv (risk-window) and thereafter. RESULTS: Out of 388,849 girls, of which 154,255 were vaccinated, 6 'confirmed' GBS cases occurred during non-exposure periods (IR of 5.83 per million person-years; 95% CI: 2.62-12.97) and 3 'confirmed' cases anytime after vaccination (IR of 7.87; 95% CI: 2.54-24.39). The resulting adjusted HR anytime after vaccination was 1.24 (95% CI: 0.19-8.00). All three cases occurred after the risk window of 90 days with an HR of 1.77 (95% CI: 0.25-12.54) for post-exposure periods as compared with non-exposure. Since zero cases occurred during the risk window, no HR could be estimated for exposed periods. CONCLUSIONS: Incidences of GBS were in line with the range previously reported for young people, supporting the potential of BIFAP for performing studies on GBS. However, a lack of power may be present for quantifying the relative risk of such a rare disease after the vaccination among the study cohort, where we can only exclude an increased risk of 8-times relative to no vaccination.
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Síndrome de Guillain-Barré , Vacunas contra la Influenza , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Estudios de Cohortes , Femenino , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/epidemiología , Humanos , Incidencia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , España/epidemiología , VacunaciónRESUMEN
PURPOSE: Hydrochlorothiazide (HCTZ) use has been linked to skin cancer in northern European countries. We assessed the association between HCTZ exposure and risk of malignant melanoma (MM) and keratinocyte carcinoma (KC) in a European Mediterranean population. METHODS: Two parallel nested case-control studies were conducted in Spain using two electronic primary healthcare databases, each one providing data on both exposure and outcomes: SIDIAP and BIFAP. Cancer cases were matched to 10 controls by age and gender through risk-set sampling. The ORs and 95% CI for MM and KC associated with previous HCTZ use were estimated using conditional logistic regression. In BIFAP, KC cases were further identified as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). RESULTS: In adjusted analyses, both ever and cumulative high (≥50,000 mg) use of HCTZ were associated with an increased risk of KC. The risk estimates for high use were 1.30 (1.26-1.34) in SIDIAP and 1.20 (1.12-1.30) in BIFAP, with a lower risk for BCC (1.11 [1.02-1.21]) than for SCC (1.71 [1.45-2.02]). A dose-response relationship was observed between cumulative doses of HCTZ and KC risk. Inconsistent results were found for high use of HCTZ and risk of MM: 1.25 (1.09-1.43) in SIDIAP and 0.85 (0.64-1.13) in BIFAP. CONCLUSIONS: In this European Mediterranean population, a high cumulative use of HCTZ was related to an increased risk of KC with a clear dose-response pattern.
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Carcinoma Basocelular , Neoplasias Cutáneas , Carcinoma Basocelular/inducido químicamente , Carcinoma Basocelular/epidemiología , Estudios de Casos y Controles , Humanos , Hidroclorotiazida/efectos adversos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología , España/epidemiologíaRESUMEN
INTRODUCTION: A link between the human papillomavirus vaccination (HPVv) and inflammatory bowel disease (IBD) has been suggested. OBJECTIVE: We aimed to estimate the risk of IBD following HPVv compared with periods not exposed to the vaccines. METHODS: Primary healthcare records (Spanish Primary Care Database For Pharmacoepidemiological Research [BIFAP]) were used in a cohort study of girls in Spain aged 9-18 years between 2007 and 2016 free of IBD or HPVv at study entrance. During the follow-up to IBD diagnosis, time-varying HPVv exposure and confounders were assessed in Cox models to estimate the hazard ratio (HRs) of IBD in the 2 years after HPVv (exposed period) and thereafter (post-exposed) compared with the no exposure periods. In a post hoc analysis, we moved the IBD date back 30 days as a theoretical delay in diagnosis confirmation. RESULTS: The cohort comprised 388,669 girls; 154,174 of these received the HPVv, and 88 IBD cases occurred (55 non-exposed, 22 exposed [after first N = 6, second N = 2, or third N = 14 dose] and 11 in post-exposed periods). The adjusted HR was 1.66 (95% confidence interval [CI] 0.68-4.05) for exposed and 1.10 (95% CI 0.37-3.24) for post-exposed periods. The HR for the first dose was 3.94 (95% CI 1.19-13.02). No association was found for the second or third doses. Post hoc, the HR was 1.83 (95% CI 0.72-4.69) for exposed periods (N = 18), and 1.84 (95% CI 0.35-9.83; N = 2), 1.50 (95% CI 0.40-5.63; N = 4) and 1.98 (95% CI 0.71-5.49; N = 12) after the first, second and third doses, respectively. CONCLUSIONS: This study did not show an increased risk of IBD following 2 years of HPVv exposure. However, an increased risk of IBD diagnosis was observed following the first vaccination dose (1-34 days), which is likely attributable to the clinical recommendation to vaccinate upon onset of IBD symptoms.
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Enfermedades Inflamatorias del Intestino , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/etiología , Masculino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Atención Primaria de Salud , España/epidemiología , Vacunación/efectos adversosRESUMEN
PURPOSE: We aimed to characterize the trends of immediate release fentanyl (IRF) use in Spain between 2012 and 2017 and indication for its use. IRF drugs are rapid-acting opioids approved to treat breakthrough cancer pain (BTCP) in patients already receiving maintenance opioid therapy for chronic cancer pain. A substantial increase in consumption of IRF has been observed with emerging cases of abuse and dependence, most of them in noncancer patients. METHODS: An ecological descriptive consumption study with aggregated data from drug dispensed by community pharmacies and reimbursed by the National Health System in which Defined Daily Doses per 10 000 inhabitants (DID) were calculated and a retrospective cohort study using data from the Spanish Database for Pharmacoepidemiological Research in Primary Care in which participants entered the cohort study after 1 year with the Primary Care Practitioners were performed. Annual prevalence and incidence rate of IRF use were estimated by sex and calendar year. Potential indication was also assessed. RESULTS: IRF use in Spain increased from 2.1 DID in 2012 to 3.8 DID in 2017. The incidence rate and prevalence increased in 53% and 74%, respectively. Patients without previous cancer or BCTP diagnosis represented 27% of incident users, predominantly women. Half of patients with noncancer-related diagnosis had a musculoskeletal disorder linked to the first IRF prescription. CONCLUSIONS: National consumption and new IRF users in Spain increased over the study period and one quarter of patients did not have a BTCP or cancer diagnosis registered in their clinical record.
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Analgésicos Opioides , Fentanilo , Estudios de Cohortes , Utilización de Medicamentos , Femenino , Humanos , Incidencia , Prevalencia , Estudios Retrospectivos , España/epidemiologíaRESUMEN
Objective: As for other auto-immune processes, thyroiditis is monitored after vaccinations. The aim was to estimate the baseline incidence of thyroiditis among girls, before investigating papillomavirus vaccination as a potential risk factor. Methods: Observational cohort study including girls aged 9-18 years and registered between 2002-2016 in the Spanish Primary Care Database for Pharmacoepidemiological Research. Girls were followed until a thyroiditis occurred, 19 years of age, left the cohort, died, or the study ended. Anonymized records were reviewed for diagnosis confirmation (endocrine discharge letter and/or free-text comments) in a random sample. Incidence rate (IR) per 105 person years (/105 py) was estimated. Results: The cohort numbered 480,169 girls, of whom 641 had a record of thyroiditis: 346 autoimmune thyroiditis; 17 thyroiditis of other types; and 278 unspecified. Incidence of recorded thyroiditis increased with age, from 23.96 at age 9 years to 47.91 at age 14 years, and stabilized around 31.06-34.43 among girls aged 15-18 years. Of the 98 records reviewed, 60.2% were 'confirmed' cases, 32.7% 'possible' and 7.1% were discarded. After correction for discarded cases, IR=20.83 'confirmed' cases, increasing to 32.12/105 py when 'confirmed' plus 'possible' cases were included. Between 2002-2005, incidences were lower (16.28 and 20.93 cases/105 py) than in the period 2007-2016 (21.17 and 33.78 cases/105 py) for 'confirmed' and 'confirmed' plus 'possible', respectively. Conclusion: Two-thirds of the recorded thyroiditis included confirmatory evidence. The incidence of thyroiditis among girls increased with age and in the later period, and remained stable among girls aged 15-18 years.
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Atención Primaria de Salud/estadística & datos numéricos , Tiroiditis/epidemiología , Adolescente , Factores de Edad , Niño , Femenino , Humanos , Incidencia , España/epidemiología , Tiroiditis Autoinmune/epidemiologíaRESUMEN
PURPOSE: Inflammatory bowel disease (IBD) recording validation among girls in the Spanish Primary Care Database For Pharmacoepidemiological Research (BIFAP). METHODS: In this observational study, girls aged 9 to 18 years registered in BIFAP between 2002 and 2016, were followed up until there was a recorded IBD diagnosis or a referral to specialist indicating IBD. Anonymized profiles were reviewed to retrieve diagnosis confirmation (a positive colonoscopy or biopsy, specialist, or physician's comments mentioning the IBD diagnosis) or discarding (negative procedure results, alternative diagnosis, or family history). "possible" IBD were profiles missing that evidence, or had suspected IBD. The prescriptions of intestinal anti-inflammatory agents, azatioprine, and mercaptopurine were collected. The prevalence of IBD was estimated after review. RESULTS: Out of 480 634 girls, 323 had a first ever recorded IBD, of which, 37.8% (N = 122) were "confirmed" incident IBD diagnosis, 19.8% (N = 64) discarded and 38.7% (N = 125) "possible" IBD. Additionally, 12 IBD records (3.7%) referred to prevalent IBD. Prescriptions were recorded in 94.3% (confirmed), 63.2% (possible), 83.3% (prevalent), and 3.1% (discarded) IBD cases. Prevalence was 52.83 "confirmed" or 93.58/105 girls when "possible" IBD were added. CONCLUSIONS: For a third of the girls, the first recorded IBD included evidence confirming the diagnosis while most of those with missing evidence had treatment indicated for IBD. For research focused in sensitivity, an algorithm including "possible" plus "confirmed" episodes is recommended, whereas only "confirmed" to guarantee higher predictive value. Prevalence suggests that IBD is not a rare disease among girls.
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Enfermedades Inflamatorias del Intestino , Registros Electrónicos de Salud , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/epidemiología , Farmacoepidemiología , Prevalencia , Atención Primaria de SaludRESUMEN
PURPOSE: In Spain, a human papillomavirus (HPV) vaccine was firstly marketed in 2006 and mainly administered in primary care (PC) practices for girls/women or schools. As for all vaccines, a valid data source is required for research on observational effectiveness or safety. The objective of this study is to identify and validate HPV vaccinations recorded among women in The Primary Care Database For Pharmacoepidemiological Research (BIFAP) from 2007. METHODS: BIFAP includes a Vaccination File filled by PC practitionners and pediatricians. Information on women with HPV vaccinations recorded at any age was identified and validated according to whether (1) doses adhered to the following standard intervals: 27 to 269 days between first and second doses, >55 days between second and third doses, and <366 between first and third doses, and (2) additional information recorded in clinical records confirmed (through recording the brand, batch, expiring date, administration site, or vaccination comment) or refuted the vaccination and date. The latter was retrieved through manual review of anonymous records randomly selected. RESULTS: One hundred seventeen thousand seventy-three women with HPV vaccination records were identified (mean age 14.7 years); 82.5% had three jabs, 87.3% in recommended intervals. A sample of 978 patients' records, including 2245 jabs, was reviewed. Of the 363 jabs with additional information, 91% confirmed the vaccination. Confirmatory data was more frequent when doses strictly adhered to recommendations (96.8%-100%) than not (60.0%-85.7%). CONCLUSIONS: In BIFAP, a cohort of women vaccinated against HPV, mostly with three doses in recommended intervals, was identified. Although additional information about the vaccination was scarce, when present, it highly confirmed it, making BIFAP a potential data source for HPV vaccine research.
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Bases de Datos Factuales/estadística & datos numéricos , Vacunación Masiva/estadística & datos numéricos , Vacunas contra Papillomavirus/administración & dosificación , Farmacoepidemiología/métodos , Atención Primaria de Salud/estadística & datos numéricos , Adolescente , Adulto , Niño , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Esquemas de Inmunización , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Farmacoepidemiología/estadística & datos numéricos , Estudios Retrospectivos , España/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adulto JovenRESUMEN
BACKGROUND: In Spain, girls are vaccinated against human papillomavirus (HPV) in the primary care setting, according to a national vaccination programme. Vaccination is voluntary and is covered by the public health system. OBJECTIVES: The aim of the study was to estimate the incidence and patterns of HPV vaccination amongst girls in primary care in Spain. METHODS: A cohort study was performed using the information recorded in the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP) from 7.9 million patients from seven Spanish regions, between 2001 and 2016 (56.6% of the regional population). Data available in BIFAP include patient age, sex, life-style factors, clinical events, specialist referrals, prescriptions, and vaccinations as recorded by the primary care physician (PCP) or administering nurse. The study cohort comprised all girls aged 9-18 years registered in BIFAP between 1st January of 2007 and 31st December of 2016 who had at least 1 year of clinical record information with their PCP (inclusion criteria). The date the inclusion criteria were met was designated as the start date to the study cohort contribution. In order to estimate the incidence of HPV vaccination (initiation of vaccination schedule), girls with an HPV vaccination recorded before the start date or without vaccination date were excluded. Girls forming the study cohort were followed from start date until there was a recorded HPV vaccination, they reached 19 years of age or died, end of available information, or 31st December 2016. The person-time of all patients forming the study cohort was reckoned in the incidence estimations. The follow-up was replicated yearly from 2007 to 2016. The cumulative incidence (CuIn) of vaccination by birth cohort, year and region, was estimated using life tables (proportion of vaccination by intervals in which the denominator is the initial population corrected for losses). RESULTS: Of 388,690 girls forming the study population, 154,211 initiated the vaccination during 2007-2016. Ages ranged from 12 to 14 years at first dose in 84.5% of vaccinated girls, 42.79% received a quadrivalent vaccine, 21.86% a bivalent vaccine, and 35.35% an unknown type. Of the vaccinated population, 48.0% were completely vaccinated with a three-dose schedule and 28.9% with a two-dose schedule, 20.2% received one dose and 3.0% two doses in a three-dose schedule, at a maximum of 10 years of follow-up. The CuIn was highest among girls aged either 13 or 14 years over all regions (reaching 92.8% and 89.7%, respectively), and aged 12 in some regions/years (up to 89.8%). Girls aged 15 years were also vaccinated (although showing lower yearly incidence, i.e. < 69.1%) in two regions. The coverage was broadened to younger girls (11 years) during the last years of the study period in some regions. CONCLUSIONS: According to BIFAP primary care data, a high incidence of vaccination among girls aged 13-14 years was observed. Vaccination among younger and older girls were less common, although they reached high incidence in some regions and/or years. Most vaccination patterns adjusted to a complete vaccination regimen, as recommended posology.
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Vacunación Masiva/estadística & datos numéricos , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Aceptación de la Atención de Salud/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Distribución por Edad , Niño , Bases de Datos Factuales/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Esquemas de Inmunización , Estudios Longitudinales , Papillomaviridae/inmunología , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/virología , Farmacoepidemiología/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , España , Neoplasias del Cuello Uterino/virología , Cobertura de Vacunación/estadística & datos numéricosRESUMEN
BACKGROUND: In Spain, girls and women are vaccinated against human papillomavirus (HPV) in the primary care setting, according to a national vaccination program. Vaccination is voluntary and the cost is covered by the public health system. OBJECTIVES: The aim of the study was to estimate the incidence and patterns of HPV vaccination amongst girls in Spain. METHODS: A cohort study was performed using the information recorded in the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP) from 7.4 million patients from eight Spanish regions, between 2001 and 2013 (56% of the regional population). Data available in BIFAP include patient age, sex, lifestyle factors, clinical events, specialist referrals, prescriptions, and vaccinations as recorded by the primary care physician (PCP) or administering nurse. The study cohort comprised all girls aged 11-18 years registered in BIFAP between 1 January 2007 and 31 December 2013 who had at least 1 year of clinical record information with their PCP (inclusion criteria). The date the inclusion criteria were met was designated as the start date of the study cohort contribution. In order to estimate the incidence of HPV vaccination, girls forming the study cohort were followed from start date until there was a recorded HPV vaccination, they reached 19 years of age or died, the end of available information, or 31 December 2013. The person-time of all patients forming the study cohort was taken into account in the incidence estimations. The cumulative incidence (CuIn) of vaccination by birth cohort, year and region was estimated using life-tables (proportion of vaccination by intervals in which the denominator is the initial population corrected for losses). RESULTS: Out of 273,098 girls forming the study population, 81,461 were vaccinated during 2007-2013. Age ranged from 12 to 14 years at first dose in 86.0% of vaccinated girls; 54.1% received a quadrivalent vaccine, 21.9% a bivalent vaccine, and 24.0% an unknown type. Out of the vaccinated population, 87.9% received three doses, 8.2% two and 3.9% one dose, at a maximum of 7 years of follow-up. By calendar year and region, the CuIn reached 70.0-95.8% for birth cohorts between 1993 and 1999, 28.6-99.0% for births cohorts between 1990 and 1992, and exceptionally, 70.6-99.8% for births cohorts between 2000 and 2002 in three regions. CONCLUSIONS: According to BIFAP primary care data, a high incidence of vaccination among girls aged 13-15 years was observed. Vaccination among younger and older girls was less common although they reached high incidence in those regions that included girls aged 11-18 years in mass programs. Most vaccination patterns adjusted to a three-dose regimen, as recommended.
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INTRODUCTION: Trazodone was authorized for the treatment of depression in the 1970s. Several additional therapeutic uses have been proposed due to its heterogeneous mechanism. This study aims to determine the use of trazodone in the elderly in Spain. METHODS: A nationwide, longitudinal and descriptive analysis was conducted using data from patients aged >65 years with a first prescription of trazodone during the period 2002-2011. Information on dose, comorbidities and relevant co-medication was gathered from the Spanish Primary Care database BIFAP. Incidence rates of trazodone use per 10,000 person-years were calculated by sex and age. RESULTS: A total of 11,766 patients receiving a first prescription of trazodone were included. The incidence rate of trazodone use was 47.2 (95% CI: 46.33-48.04) per 10,000 person-years. An increasing trend in the use of trazodone was observed (5-fold increase in 2011 as compared to 2002). The most common therapeutic indications were: depression (21.41%), Alzheimer/dementia (20.36%), sleep disorders (16.22%), and anxiety disorder (8.91%). The median dose was 100mg/day. The use of trazodone concomitantly with interacting medicines was frequent: anti-hypertensives (53.60%), and CNS depressors (59.32%). CONCLUSIONS: Trazodone use is increasing in elderly patients, and a high proportion of use in non-approved indications was observed. Trazodone is not being used at high doses, but interacting medicines were frequent, and it may pose additional risks for elderly patients.
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Antidepresivos de Segunda Generación/uso terapéutico , Utilización de Medicamentos/tendencias , Pautas de la Práctica en Medicina/tendencias , Trazodona/uso terapéutico , Anciano , Anciano de 80 o más Años , Trastornos de Ansiedad/tratamiento farmacológico , Bases de Datos Factuales , Demencia/tratamiento farmacológico , Depresión/tratamiento farmacológico , Esquema de Medicación , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , Masculino , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud , Trastornos del Sueño-Vigilia/tratamiento farmacológico , EspañaRESUMEN
OBJECTIVE: Different regulatory actions for anti-osteoporotic medication (AOM) were taken during the last years, including marketing of new drugs, safety warnings, or restrictions on the indications. We aimed to characterise the secular trends of AOM use in Spain from 2001 to 2013. METHODS: A cohort study using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP), was performed. BIFAP includes anonym records for 4million patients. Participants entered the study when aged ≥50years in 2001-2013 and after 1year of data available, and were followed to an AOM prescription (including alendronate, other bisphosphonates, SERM (selective estrogen receptor modulators), strontium ranelate, teriparatide or denosumab), death, lost or the end of December 2013. Prevalence (%) and incidence rate (IR/1000person-years (py)) of AOM users were computed by years and sex. RESULTS: Out of 1.5million participants, 135,410 received AOM treatment during 2001-2013. Prevalence was 6.1% (women) and 1.1% (men), that increased from 2001 (2.0%) to 2009 (7.6%) to decrease thereafter. Out of them, 95,057 were incident. The IR was 24.90 (women) and 2.77 (men), that increased from 2001 (21.25 and 1.96) to 2007 (35.84 and 3.64), and decreased to 12.48 and 1.81 (2013). IRs were highest for bisphosphonates along the years (ranging 3.70-14.73 and 0.57-1.75 in women and men respectively), followed by SERM up to 2005 (6.51-9.02 and 0.06-0.07), and strontium ranelate from 2006 (4.66 and 0.45) to 2012 (2.05 and 0.26). IR for teriparatide increased from marketing in 2004 (0.10-1.01 and 0.02-0.29), as was denosumab from marketing in 2011 (0.03-2.64 and 0.09-0.15). CONCLUSIONS: Population-based estimates of AOM use in Spain peaked in 2007-2009 and decreased thereafter, irrespective of age and sex. New treatments were ten times higher in women than men. Bisphosphonates were the most frequently prescribed class, followed by SERM in women before 2006, strontium otherwise till 2012, and denosumab in women or teriparatide in men in 2013. Changes in the osteoporosis criteria, fracture risk assessment strategies, and regulatory actions for AOM around the time, may explain that trend.
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Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Osteoporosis/epidemiología , Prevalencia , España/epidemiologíaRESUMEN
Among 95,057 patients ≥50 years with new anti-osteoporosis medications (AOM) (2001-2013) in primary care, 1-year cessation was 51% (28%-68%), higher in men, smokers, patients with missing lifestyle data, and out normal BMI, and lower in those aged 60-79, with recent fractures or other anti-osteoporotics, suggesting non-severe osteoporosis and less risk awareness. PURPOSE: Low compliance to anti-osteoporosis medications (AOM) has been previously reported. We aimed to estimate 1-year cessation rates of different AOMs as used in Spanish healthcare settings, and to identify associated risk factors. METHODS: A cohort study was performed using primary care records data (BIFAP). Patients entered the cohort when aged 50 years in 2001-2013, with ≥1 year of data available, and identified as incident users of AOM (1-year washout). Participants were divided into six cohorts: alendronate, other oral bisphosphonates, selective oestrogen receptor modulators, strontium ranelate, teriparatide, and denosumab. Patients were followed from therapy initiation to the earliest of cessation (90-day refill gap), switching (to alternative AOM), loss to follow-up, death, or end of 2013. One-year therapy cessation was estimated using life tables. Hazard ratios (of cessation) according to age, sex, lifestyle factors, morbidity, and co-medication were estimated after stepwise backwards selection. RESULTS: A total of 95,057 AOM users were identified (91% women; mean age 68). One-year cessation was 51% overall, highest for strontium ranelate (68%), and lowest for denosumab (28%). Cessation probability was higher in men (14% to 2.1-fold), smokers (>6%), and patients with missing BMI (19-28%) or smoking (6-20%) data, and overweight/obese/underweight (7% to 2.6-fold increase compared to normal weight). Patients aged 60-79 years, with a recent fracture or other drugs used for osteoporosis, had better persistence. CONCLUSIONS: Over half of the patients initiating AOM stopped therapy within the first year after initiation. The described risk factors for cessation could be proxies for non-severe osteoporosis, and/or disease/risk awareness, which could inform the targeting of high-risk patients for monitoring and/or interventions aimed at improving persistence.
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Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis/tratamiento farmacológico , Atención Primaria de Salud/estadística & datos numéricos , Privación de Tratamiento/estadística & datos numéricos , Anciano , Alendronato/uso terapéutico , Estudios de Cohortes , Denosumab/uso terapéutico , Femenino , Fracturas Óseas/etiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , España , Teriparatido/uso terapéutico , Tiofenos/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVE: The objective of the study was to describe the trends of utilization, supply and prevalence of hormone replacement therapy (HRT) in Spain during the period 2000-2014. METHODS: Annual prevalence of HRT use including the 95% CI was calculated for women aged≥40 using individual data from the national population-based database BIFAP. Annual and total-period consumptions were expressed in defined daily doses (DDD) per 1,000 inhabitants per day and were obtained from the databases of medications dispensed in community pharmacies and charged through official prescriptions to the Spanish National Health System. RESULTS: In the year 2000, overall HRT consumption was 33.12 DDDs/1000 inhabitans/day: 19.81 for oestrogen only, 6.88 for tibolone and 6.44 for combined oestrogen and progestagen. In 2014 overall HRT consumption was 5.32 DDDs/1000 inhabitans/day: 1.08 for oestrogen only, 1.61 for tibolone and 2.62 for combinations of oestrogen and progestagen. The marketed presentations of HRT decreased by 46.9%. Prevalence of HRT use in women aged≥40 in BIFAP was 7.19% (95% CI 6.97-7.40) in 2001 and 0.21% (95% CI 0.20-0.22) in 2014. Women aged 40-45 registered the highest prevalence of use in 2014: 0.71% (95% CI 0.66-0.76). CONCLUSIONS: A sharp decline in the consumption and prevalence of HRT has been observed in Spain since the publication of the Women's Health Initiative and Million Women Study and the regulatory measures taken restricting conditions of use, showing a similar trend to that of other western countries.
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Antagonistas de Andrógenos/uso terapéutico , Estrógenos/uso terapéutico , Terapia de Reemplazo de Hormonas/estadística & datos numéricos , Menopausia , Norpregnenos/uso terapéutico , Pautas de la Práctica en Medicina/tendencias , Progestinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Quimioterapia Combinada , Femenino , Terapia de Reemplazo de Hormonas/tendencias , Humanos , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , EspañaRESUMEN
BACKGROUND: Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes. METHODS AND FINDINGS: Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints. CONCLUSIONS: In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment. REVIEW REGISTRATION: PROSPERO CRD42014014404.