[Response to the COVID-19 Health Crisis from a Gender Perspective: Lessons Learned]. / Respuesta a la crisis sanitaria de la COVID-19 desde la perspectiva de género: lecciones aprendidas.

OBJECTIVE: To delve deeper from a gender perspective into the lessons learned during the COVID-19 pandemic to address future health crises. METHOD: Study with key informants with experience in public health and gender from the Ministerio de Sanidad, ministries of the autonomous communities, Institut Català de la Salut, Hospital de La Princesa, Escuela Andaluza de Salud Pública and Universidad País Vasco. SOURCE OF INFORMATION: individual open-ended questionnaire on health and health inequalities/gender inequalities related to COVID-19. After presenting the findings, the key informants group discussed them in a meeting until reaching a consensus on the lessons learned. RESULTS: The lack of clinical statistics by sex could compromise epidemiological surveillance, losing the opportunity to characterize the disease. The performance of essential services fell more on women, exhausting them with double and triple shifts; with the differences according to sex in the clinical presentation of COVID-19, and the criteria for hospitalization/admission to the intensive care unit, their access to health care decreased. Increased: gender violence and mental health problems; delaying recognition of the second effects of vaccines in women; partially due to information biases in clinical trials. The gender perspective was lacking in academic, healthcare, and health management areas. CONCLUSIONS: Women's gender dimensions determined their higher frequency of COVID-19 and played a fundamental role in its control. Broadly considering the lessons learned will strengthen prevention systems and be able to provide effective responses to future health crises.

Respuesta a la crisis sanitaria de la COVID-19 desde la perspectiva de género: lecciones aprendidas / Response to the COVID-19 Health Crisis from a Gender Perspective: Lessons Learned

Objetivo: Profundizar desde la perspectiva de género en las lecciones aprendidas durante la pandemia de COVID-19 para hacer frente a futuras crisis de salud. Método: Estudio con informantes clave con experiencia en salud pública y género del Ministerio de Sanidad, Consejerías de las comunidades autónomas, Institut Català de la Salut, Hospital de La Princesa, Escuela Andaluza de Salud Pública y Universidad del País Vasco. Fuente de información: cuestionario individual de respuestas abiertas sobre inequidades o desigualdades de género sanitarias y en salud relacionadas con la COVID-19. Tras presentar los hallazgos, el grupo de informantes clave se reunió y debatió hasta llegar a un consenso sobre las lecciones aprendidas. Resultados: La falta de estadísticas clínicas por sexo pudo comprometer la vigilancia epidemiológica, perdiendo una oportunidad para caracterizar la enfermedad. El desempeño de los servicios esenciales recayó más en las mujeres, extenuándolas con dobles y triples jornadas, lo cual, junto con las diferencias según sexo en la presentación clínica de la COVID-19 y los criterios de hospitalización y de ingreso en la unidad de cuidados intensivos, disminuyó su acceso a la atención sanitaria. Aumentaron la violencia de género y los problemas de salud mental, retrasando el reconocer los efectos secundarios de las vacunas en las mujeres parcialmente por sesgos de información en los ensayos clínicos. La perspectiva de género faltó en los ámbitos académicos, asistenciales y de gestión sanitaria. Conclusiones: Las dimensiones de género de las mujeres determinaron su mayor frecuencia de COVID-19 y desempeñaron un papel fundamental en su control. Considerar las lecciones aprendidas fortalecerá los sistemas de prevención y permitirá poder dar respuestas eficaces a futuras crisis de salud.(AU)

Objective: To delve deeper from a gender perspective into the lessons learned during the COVID-19 pandemic to address future health crises. Method: Study with key informants with experience in public health and gender from the Ministerio de Sanidad, ministries of the autonomous communities, Institut Català de la Salut, Hospital de La Princesa, Escuela Andaluza de Salud Pública and Universidad País Vasco. Source of information: individual open-ended questionnaire on health and health inequalities/gender inequalities related to COVID-19. After presenting the findings, the key informants group discussed them in a meeting until reaching a consensus on the lessons learned. Results: The lack of clinical statistics by sex could compromise epidemiological surveillance, losing the opportunity to characterize the disease. The performance of essential services fell more on women, exhausting them with double and triple shifts; with the differences according to sex in the clinical presentation of COVID-19, and the criteria for hospitalization/admission to the intensive care unit, their access to health care decreased. Increased: gender violence and mental health problems; delaying recognition of the second effects of vaccines in women; partially due to information biases in clinical trials. The gender perspective was lacking in academic, healthcare, and health management areas. Conclusions: Women's gender dimensions determined their higher frequency of COVID-19 and played a fundamental role in its control. Broadly considering the lessons learned will strengthen prevention systems and be able to provide effective responses to future health crises.(AU)

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.

[Non-inferiority studies efficacy and safety: review of methodological and statistical aspects in clinical trials and non-interventional studies with medicinal products.] / Estudios de no inferioridad de eficacia y seguridad: revisión e interpretación de aspectos metodológicos y estadísticos en ensayos clínicos y estudios observacionales con medicamentos.

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.

Estudios de no inferioridadde eficacia y seguridad: revisión e interpretación de aspectosmetodológicos y estadísticosen ensayos clínicos y estudiosobservacionales con medicamentos / Non-inferiority studies efficacy and safety: review of methodological and statistical aspects in clinical trials and non-interventional studies with medicinal products

Los estudios de no inferioridad son cada vez más frecuentes para introducir nuevos medicamentos en el mercado. Aunque existensituaciones en las que su uso está justificado, no existe un enfoque analítico único y conservador. Para arrojar resultados fiables y decalidad, deben seguir una estricta metodología, tanto en la ejecución como en la difusión de los resultados, la cual permita, tanto alas agencias reguladoras como a los clínicos, establecer conclusiones válidas y decisiones que repercutan en beneficio de la prácticaclínica. La mayor parte de las revisiones publicadas se centran en los ensayos clínicos de no inferioridad de eficacia. En esta revisiónse contemplan, además, los diseños observacionales y los aspectos específicos de los estudios de seguridad. Todo ello desde unpunto de vista práctico y sencillo, con un contenido matemático mínimo.(AU)

Non-inferiority studies are increasingly more common for introducing new medicines in the market. Despite being situations wherethe use of this study design is justified, there is not a common analytical approach on how to conduct them. Pursuing a rigorousmethodology, both in the study conduction and in its disseminations, is critical to ensure robust results to enable regulatory agenciesand clinicians to reach valid conclusions and decisions which ultimately will benefit clinical practice. Most of the published reviewsfocus on the efficacy outcomes of non-inferiority clinical trials. We are unaware of other reviews that goes beyond and includes spe-cific aspects for non-interventional designs and for studies focused on safety. Moreover, this review provides a simple and practicalperspective with a minimum mathematical content on this complex type of studies.(AU)

Selective Serotonin Reuptake Inhibitors and Risk of Noncardioembolic Ischemic Stroke: A Nested Case-Control Study.

BACKGROUND: Multiple studies have reported that the use of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased risk of ischemic stroke; however, this finding may be the result of a confounding by indication. We examined the association using different approaches to minimize such potential bias. METHODS: A nested case-control study was carried out in a Spanish primary health-care database over the study period 2001 to 2015. Cases were patients sustaining an ischemic stroke with no sign of cardioembolic or unusual cause. For each case, up to 5 matched controls (for exact age, sex, and index date) were randomly selected. Antidepressants were divided in 6 pharmacological subgroups according to their mechanism of action. The current use of SSRIs (use within a 30-day window before index date) was compared with nonuse, past use (beyond 365 days) and current use of other antidepressants through a conditional logistic regression model to obtain adjusted odds ratios and 95% CI. Only initiators of SSRIs and other antidepressants were considered. RESULTS: A total of 8296 cases and 37 272 matched controls were included. Of them, 255 (3.07%) were current users of SSRIs among cases and 834 (2.24%) among controls, yielding an adjusted odds ratio of 1.14 (95% CI, 0.97-1.34) as compared with nonusers, 0.94 (95% CI, 0.77-1.13) as compared with past-users and 0.74 (95% CI, 0.58-0.93) as compared with current users of other antidepressants. No relevant differences were found by duration (≤1, >1 year), sex, age (<70, ≥70 years old) and background vascular risk. CONCLUSIONS: The use of SSRIs was not associated with an increased risk of noncardioembolic ischemic stroke. On the contrary, as compared with other antidepressants, SSRIs appeared to be protective.

Effect of regulatory interventions on agomelatine use in Spain: A multiple intervention time-series analysis in a nationwide electronic healthcare record database.

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.

Drug utilization study on immediate release Fentanyl in Spain. Prevalence, incidence, and indication.

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.

Differential effects of antidepressant subgroups on risk of acute myocardial infarction: A nested case-control study.

The primary objective of this study was to investigate the association between antidepressants use and the risk of acute myocardial infarction (AMI). METHODS: We conducted a nested case-control study using a primary care database over the period 2002-2015. From a cohort of patients aged 40-99 years, we identified incident AMI cases and randomly selected 5 controls per case, matched to cases for exact age, sex and index date. Exposure to antidepressants were categorised as current, recent, past and nonusers. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were computed using conditional logistic regression to assess the association between the current use of different antidepressants subgroups and AMI as compared to nonuse. Dose and duration effects were explored. RESULTS: Totals of 24 155 incident AMI cases and 120 775 controls were included. The current use of antidepressants as a group was associated with a reduced risk (AOR = 0.86; 95% CI: 0.81-0.91), but mainly driven by selective serotonin reuptake inhibitors (AOR = 0.86; 95% CI:0.81-0.93). A reduced risk was also observed with trazodone (AOR = 0.76;95% CI: 0.64-0.91), and clomipramine (AOR = 0.62; 95% CI: 0.40-0.96), whereas no significant effect was observed with other antidepressants. A duration-dependent effect was suggested for selective serotonin reuptake inhibitors, trazodone and clomipramine, while there was no clear dose-dependency. CONCLUSION: This study suggests that current use of antidepressants interfering selectively with the reuptake of serotonin, and those antagonizing the 5-HT2A receptor, are associated with a decrease in AMI risk and should be the antidepressants of choice in patients at cardiovascular risk.

Risk of Myocardial Infarction Among New Users of Calcium Supplements Alone or Combined With Vitamin D: A Population-Based Case-Control Study.

A population-based case-control study was conducted to evaluate the risk of acute myocardial infarction among new users of calcium supplements either in monotherapy (CaM) or in combination with vitamin D (CaD). A total of 23,025 cases and 114,851 controls randomly sampled from the underlying cohort and matched with cases by age, sex, and index date were included. New users of CaM and CaD were categorized as current users, recent users, past users, and nonusers. We computed adjusted odds ratios (AORs) and their 95% confidence intervals (CIs) among current users as compared with nonusers through a conditional logistic regression. No increased risk was associated with CaM overall (59 cases (0.26%) and 273 controls (0.24%); AOR = 0.80; 95% CI 0.59-1.09), nor was it found in any of the conditions examined. Instead, the use of CaD was associated with a decreased risk (275 cases (1.19%) and 1,160 controls (1.45%); AOR = 0.78; 95% CI 0.67-0.90), dose and duration-dependent, and particularly evident in patients with a high cardiovascular risk (AOR = 0.59; 95% CI 0.43-0.81).

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.

The reason for having a code of pharmaceutical ethics: Spanish Pharmacists Code of Ethics / El porqué de un código de ética farmacéutica: Código Español de Ética Farmacéutica

The pharmacist profession needs its own code of conduct set out in writing to serve as a stimulus to pharmacists in their day-to-day work in the different areas of pharmacy, in conjunction always with each individual pharmacist´s personal commitment to their patients, to other healthcare professionals and to society. An overview is provided of the different codes of ethics for pharmacists on the national and international scale, the most up-to-date code for 2015 being presented as a set of principles which must guide a pharmacutical conduct from the standpoint of deliberative judgment. The difference between codes of ethics and codes of practice is discussed. In the era of massive-scale collaboration, this code is a project holding bright prospects for the future. Each individual pharmacutical attitude in practicing their profession must be identified with the pursuit of excellence in their own personal practice for the purpose of achieving the ethical and professional values above and beyond complying with regulations and code of practice (AU)

Se necesita un código de conducta propio y escrito, que dinamice la realidad de la profesión farmacéutica en el trabajo cotidiano en sus distintas áreas, siempre como un compromiso individual del farmacéutico con el paciente, con otros profesionales sanitarios y con la sociedad. Se hace una panorámica de los diversos códigos de ética farmacéutica a nivel nacional e internacional, presentando el más actualizado, de 2015, como un conjunto de principios que debe guiar el comportamiento del farmacéutico desde la prudencia deliberativa. Se plantea la diferencia ante los códigos de ética y deontología. En la era de la colaboración masiva, el código es un proyecto de futuro de oportunidades. La actitud del farmacéutico en su ejercicio profesional deberá identificarse con la búsqueda de la excelencia en la práctica individual, que tiene como objetivo alcanzar los valores éticos y profesionales que van más allá del cumplimiento de la normativa legal y los códigos deontológicos (AU)

The reason for having a code of pharmaceutical ethics: Spanish Pharmacists Code of Ethics.

The pharmacist profession needs its own code of conduct set out in writing to serve as a stimulus to pharmacists in their day-to-day work in the different areas of pharmacy, in conjunction always with each individual pharmacist´s personal commitment to their patients, to other healthcare professionals and to society. An overview is provided of the different codes of ethics for pharmacists on the national and international scale, the most up-to-date code for 2015 being presented as a set of principles which must guide a pharmacutical conduct from the standpoint of deliberative judgment. The difference between codes of ethics and codes of practice is discussed. In the era of massive-scale collaboration, this code is a project holding bright prospects for the future. Each individual pharmacutical attitude in practicing their profession must be identified with the pursuit of excellence in their own personal practice for the purpose of achieving the ethical and professional values above and beyond complying with regulations and code of practice.

Se necesita un código de conducta propio y escrito, que dinamice la realidad de la profesión farmacéutica en el trabajo cotidiano en sus distintas áreas, siempre como un compromiso individual del farmacéutico con el paciente, con otros profesionales sanitarios y con la sociedad. Se hace una panorámica de los diversos códigos de ética farmacéutica a nivel nacional e internacional, presentando el más actualizado, de 2015, como un conjunto de principios que debe guiar el comportamiento del farmacéutico desde la prudencia deliberativa. Se plantea la diferencia ante los códigos de ética y deontología. En la era de la colaboración masiva, el código es un proyecto de futuro de oportunidades. La actitud del farmacéutico en su ejercicio profesional deberá identificarse con la búsqueda de la excelencia en la práctica individual, que tiene como objetivo alcanzar los valores éticos y profesionales que van más allá del cumplimiento de la normativa legal y los códigos deontológicos.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses.

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.

The quality of reporting methods and results of cost-effectiveness analyses in Spain: a methodological systematic review.

BACKGROUND: Cost-effectiveness analysis has been recognized as an important tool to determine the efficiency of healthcare interventions and services. There is a need for evaluating the reporting of methods and results of cost-effectiveness analyses and establishing their validity. We describe and examine reporting characteristics of methods and results of cost-effectiveness analyses conducted in Spain during more than two decades. METHODS: A methodological systematic review was conducted with the information obtained through an updated literature review in PubMed and complementary databases (e.g. Scopus, ISI Web of Science, National Health Service Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases from Centre for Reviews and Dissemination (CRD), Índice Médico Español (IME) Índice Bibliográfico Español en Ciencias de la Salud (IBECS)). We identified cost-effectiveness analyses conducted in Spain that used quality-adjusted life years (QALYs) as outcome measures (period 1989-December 2014). Two reviewers independently extracted the data from each paper. The data were analysed descriptively. RESULTS: In total, 223 studies were included. Very few studies (10; 4.5 %) reported working from a protocol. Most studies (200; 89.7 %) were simulation models and included a median of 1000 patients. Only 105 (47.1 %) studies presented an adequate description of the characteristics of the target population. Most study interventions were categorized as therapeutic (189; 84.8 %) and nearly half (111; 49.8 %) considered an active alternative as the comparator. Effectiveness of data was derived from a single study in 87 (39.0 %) reports, and only few (40; 17.9 %) used evidence synthesis-based estimates. Few studies (42; 18.8 %) reported a full description of methods for QALY calculation. The majority of the studies (147; 65.9 %) reported that the study intervention produced "more costs and more QALYs" than the comparator. Most studies (200; 89.7 %) reported favourable conclusions. Main funding source was the private for-profit sector (135; 60.5 %). Conflicts of interest were not disclosed in 88 (39.5 %) studies. CONCLUSIONS: This methodological review reflects that reporting of several important aspects of methods and results are frequently missing in published cost-effectiveness analyses. Without full and transparent reporting of how studies were designed and conducted, it is difficult to assess the validity of study findings and conclusions.

Prescripción de fármacos antihipertensivos: ¿en el buen camino? Respuesta / Antihypertensive medication: on the right path? response

No disponible

Equipoise clínico y revisiones sistemáticas de ensayos clínicos aleatorizados controlados / Clinical equipoise and systematic reviews of randomized controlled trials

No disponible

Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: Systematic review and meta-analysis of randomized controlled trials / Riesgo de tromboembolismo con agonistas del receptor de la trombopoyetina en pacientes adultos con trombocitopenia: revisión sistemática y metaanálisis de ensayos clínicos aleatorizados y controlados

Background and objective: Romiplostim and eltrombopag are thrombopoietin receptor (TPOr) agonists that promote megakaryocyte differentiation, proliferation and platelet production. In 2012, a systematic review and meta-analysis reported a non-statistically significant increased risk of thromboembolic events for these drugs, but analyses were limited by lack of statistical power. Our objective was to update the 2012 meta-analysis examining whether TPOr agonists affect thromboembolism occurrence in adult thrombocytopenic patients. Materials and methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Updated searches were conduced on PubMed, Cochrane Central, and publicly available registries (up to December 2014). RCTs using romiplostim or eltrombopag in at least one group were included. Relative risks (RR), absolute risk ratios (ARR) and number needed to harm (NNH) were estimated. Heterogeneity was analyzed using Cochran's Q test and I2 statistic. Results: Fifteen studies with 3026 adult thrombocytopenic patients were included. Estimated frequency of thromboembolism was 3.69% (95% CI: 2.95–4.61%) for TPOr agonists and 1.46% (95% CI: 0.89–2.40%) for controls. TPOr agonists were associated with a RR of thromboembolism of 1.81 (95% CI: 1.04–3.14) and an ARR of 2.10% (95% CI: 0.03–3.90%) meaning a NNH of 48. Overall, we did not find evidence of statistical heterogeneity (p = 0.43; I2 = 1.60%). Conclusions: Our updated meta-analysis suggested that TPOr agonists are associated with a higher risk of thromboemboembolic events compared with controls, and supports the current recommendations included in the European product information on this respect (AU)

Fundamento y objetivo: Los agonistas del receptor de la trombopoyetina (TPOr) (romiplostim y eltrombopag) promueven la diferenciación megacariocítica, la proliferación y la producción de plaquetas. En 2012, una revisión sistemática y metaanálisis informó de un aumento no estadísticamente significativo del riesgo tromboembólico para estos medicamentos, pero los análisis presentaban limitaciones por la falta de potencia estadística. El objetivo es actualizar el metaanálisis de 2012 examinando si los agonistas del TPOr afectan a la incidencia de tromboembolismos en los pacientes adultos con trombocitopenia. Material y métodos: Se llevó a cabo una revisión sistemática y metaanálisis de ensayos clínicos aleatorizados y controlados (ECA). Se actualizaron búsquedas llevadas a cabo en PubMed, Cochrane Central, y registros públicos (hasta Diciembre de 2014). Se incluyeron ECA en los que se administrara romiplostim o eltrombopag en al menos uno de los grupos de pacientes tratados. Se calcularon los riesgos relativos (RR), la diferencia absoluta de riesgo (ARR, por sus siglas en inglés) y el número necesario de pacientes para dañar (NNH). Se examinó la heterogeneidad estadística mediante la Q de Cochran y el estadístico I2. Resultados: Se incluyeron 15 estudios con 3026 pacientes adultos diagnosticados de trombocitopenia. Las frecuencias de acontecimientos tromboembólicos fueron de 3.69% ([intervalo de confianza] IC del 95%: 2,95–4,61%) para los agonistas del TPOr y de 1,46% (IC95%: 0,89–2,40%) para los controles. Los agonistas del TPOr se asociaron con un riesgo relativo de tromboembolismo de 1,81 (IC95%: 1,04–3,14) y una ARR del 2,10% (IC95%: 0,03–3,90%), que significa un NNH de 48. En general, no se encontró evidencia de heterogeneidad estadística (p = 0,43; I2 = 1,60%). Conclusiones: El metaanálisis actualizado sugiere que los agonistas del TPOr están asociados con un mayor riesgo de eventos thromboembólicos en comparación con los controles. Estos resultados apoyan las precauciones incluidas en la información del medicamento en la Unión Europea en relación con el riesgo tromboembólico (AU)

Uso de medicamentos antihipertensivos en España: tendencias nacionales en el periodo 2000-2012 / Use of antihypertensive drugs in Spain: National trends from 2000 to 2012

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