Características clínicas y laborales de los trabajadores de un hospital universitario con signos y síntomas de COVID-19 durante la pandemia / Clinical and occupational characteristics of university hospital workers with COVID-19 signs and symptoms during the pandemic

Objetivo: conocer las características sociodemográficas, laborales y la exposición al riesgo en trabajadores de un hospital universitario que presentaron síntomas COVID-19 durante la primera ola de la pandemia. Métodos: estudio transversal (julio-septiembre 2020) a personal del Hospital Puerta de Hierro Majadahonda (Madrid, España) que trabajó en la primera ola de la pandemia. Se diseñó una encuesta ad hoc, que incluía: perfil del trabajador, síntomas COVID-19, exposición, curso clínico y atención sanitaria, entre otros. Se realizó un análisis descriptivo. Se usó Chi cuadrado y t de Student para el contraste de hipótesis. Resultados: 992 sujetos. El 34,3% (n= 340) presentó síntomas COVID-19. 283 (84,0%) eran mujeres. El 82,9% (n= 282), personal sanitario. El 36,8% (n= 125), enfermeras. El 63,5% (n= 216) trabajó en unidades de alto riesgo. El 36,2% (n= 123) tenía patología previa. El 83,3% (n= 194) reconoció haber trabajado previamente en unidades de alto riesgo. El 84,5% (n= 229) manifestó haberse sentido expuesto a la infección durante el trabajo. El 49,7% (n= 98) tuvo alguna incidencia de riesgo. El 73,7% (n= 202) presentó astenia. Hubo mayor prevalencia de personal sanitario con síntomas COVID-19 frente a no sanitario en función del trabajo asistencial (92,9% frente a 50,0%; p< 0,001), área de trabajo COVID-19 (74,2% frente a 48,1%; p< 0,001), actividad en Unidades de riesgo alto (73,4% frente a 15,5%; p< 0,001). Conclusiones: entre trabajadores con síntomas COVID hubo una mayor proporción de personal sanitario, mujeres, enfermeras, trabajadores en áreas COVID-19, unidades de riesgo, con exposición previa con pacientes infectados/sospecha. Las diferencias entre trabajadores sanitarios y no sanitarios vienen determinadas por el lugar de trabajo durante la pandemia y el riesgo de exposición a la COVID-19.(AU)

Objective: to understand the sociodemographic and occupational characteristics and risk exposure among workers of a university hospital who presented COVID-19 symptoms during the first wave of the pandemic. Methods: a cross-sectional study (July to September 2020), on staff from the Hospital Puerta de Hierro Majadahonda (Madrid, Spain) who were working during the first wave of the pandemic. An ad hoc survey was designed, which included the worker profile, COVID-19 symptoms, exposure, clinical course, and healthcare, among others. Descriptive analysis was conducted, and Chi-square and Student’s t-test were used for statistical hypothesis testing. Results: the study included 992 subjects; 34.3% (n= 340) presented COVID-19 symptoms; 283 (84.0%) were female; 82.9% (n= 282) of them were healthcare staff; 36.8% (n= 125) were nurses; 63.5% (n= 216) worked at high risk units; 36.2% (n= 123) had a previous medical condition. Of the participants, 83.3% (n= 194) admitted having worked previously at high risk units; 84.5% (n= 229) stated that they have felt exposed to the infection during work; 49.7% (n= 98) had some incidence of risk; and 73.7% (n= 202) presented asthenia. There was a higher prevalence of healthcare staff with COVID symptoms vs. non-healthcare staff, based on care activities (92.9% vs. 50.0%; p< 0.001), work at COVID areas (74.2% vs. 48.1%; p< 0.001), and activity in high risk Units (73.4% vs. 15.5%; p< 0.001). Conclusions: among the workers with COVID symptoms, there was a higher proportion of healthcare staff, women, nurses, workers at COVID areas, risk units, and previous exposure to patients with confirmed or suspected infection. Differences between healthcare and non-healthcare staff were determined by their place of work during the pandemic and their risk of exposure to COVID-19.(AU)

Factores asociados con los signos y síntomas de COVID-19 en los profesionales sanitarios de un hospital universitario español durante la pandemia / Factors associated with covid-19 signs and symptoms in healthcare professionals at a spanish university hospital during the pandemic

Objetivos: El objetivo del estudio fue identificar los factores asociados al desarrollo de COVID-19 en profesionales sanitarios de un hospital universitario al inicio de la pandemia. Material y Métodos: Estudio transversal mediante encuesta online validada en aspecto y contenido, pre-test cognitivo y pilotaje dirigida a los profesionales sanitarios. Se describieron las frecuencias absolutas y relativas para variables cualitativas y cuantitativas, se analizaron las asociaciones mediante la prueba chi-cuadrado para cualitativas y t de Student para cuantitativas. Se realizó una regresión logística para identificar los factores asociados a la COVID-19 en profesionales sanitarios. Resultados: Participaron 728 sujetos. Se observaron diferencias estadísticamente significativas en el tipo de trabajo (p=0,041), exposición relacionada con los espacios y la organización (p=0,001), patología previa (p=0,029) y asma (p=0,034). Los profesionales sanitarios que trabajaron en áreas asistenciales del hospital presentaron la mayor probabilidad de desarrollar COVID-19 (OR: 2,02; p=0,027) y también en aquellos con exposición relacionada con los espacios y organización (OR: 2,13; p≤0,001). Conclusión: Los profesionales sanitarios que trabajaron en áreas asistenciales del hospital presentaron el doble de probabilidad de desarrollar COVID-19. Lo mismo se observó para aquellos con exposición relacionada con los espacios. (AU)

Objectives: The aim of the study was to identify factors associated with the development of COVID-19 in healthcare professionals at a university hospital at the onset of the pandemic. Material and Methods: Cross-sectional study using an online survey validated in aspect and content, cognitive pre-test and piloting aimed at healthcare professionals. Absolute and relative frequencies were described for qualitative and quantitative variables, associations were analyzed using the chi-square test for qualitative variables and Student's t-test for quantitative variables. Logistic regression was performed to identify factors associated with COVID-19 in healthcare professionals. Results: 728 workers participated in the survey. Statistically significant differences were observed in type of work (p=0.041), exposure related to spaces and organisation (p=0.001), previous pathology (p=0.029) and asthma (p=0.034). Healthcare professionals working in care areas of the hospital were most likely to develop COVID-19 (OR: 2.02; p=0.027) and also in those with exposure related to space and organisation (OR: 2.13; p≤0.001). Conclusion: Healthcare professionals who worked in care areas of the hospital were twice as likely to develop COVID-19. The same was observed for those with space-related exposure. (AU)

Drug-induced Sudden Death: A Scoping Review.

BACKGROUND: The risk of sudden cardiac death (SCD) can be increased with the use of drugs. However, it has been described heterogeneously in the literature. OBJECTIVE: This study aims to systematically review epidemiological studies dealing with druginduced sudden death, describe their methodologies, and summarize the results found. METHODS: A scoping review has been carried out using Medline electronic database. The search was limited up to 2020. Epidemiological studies were included, and case reports or case series were excluded. RESULTS: Out of 3,114 potential articles, 74 were included. Most studies originated from North America (40.5%) or Europe (39.2%). Case-control (47.3%) or cohort (40.5%) studies were the most common designs. The data for outcomes and exposure were retrieved mainly from administrative databases (37.8%) or medical charts/hospital discharge reports (32.4%), but most studies used several sources of information. A composite variable of sudden death or SCD, mainly with ventricular arrhythmia, was the most frequently used endpoint. Only 18.9% of the studies included autopsy results to confirm the death. Psychotropic drugs were the most frequently studied. An increased risk of different outcomes for typical antipsychotics, tricyclic antidepressants, domperidone, and antiepileptics is suggested. CONCLUSION: The methodologies used were highly heterogeneous, and the results were, in general, not conclusive. An improvement of the methodologies is needed to achieve a conclusion regarding the risk of SCD associated with drug use.

Riesgo de exposición a la Covid-19 en auxiliares de enfermería, enfermeras y médicos de un hospital universitario ante la pandemia / Risk of exposure to Covid-19 in nursing assistants, nurses, and physicians in a university hospital in the face of pandemic

Objetivo principal: Los profesionales sanitarios fueron los trabajadores más afectados por Covid-19, especialmente durante las primeras oleadas. El objetivo del estudio es evaluar la percepción del riesgo de exposición al Covid-19, información recibida y participación laboral entre enfermeros, médicos y auxiliares de enfermería. Metodología: Se realizó un estudio transversal mediante una encuesta epidemiológica entre enfermeras, médicos y auxiliares de enfermería de un hospital universitario. Se realizó una validación de aspecto y contenido, un pretest cognitivo y un pilotaje de la encuesta epidemiológica con treinta sujetos. Se realizó un análisis descriptivo utilizando media y desviación estándar (DE) para las variables cuantitativas y las frecuencias absolutas (n) y relativas (%) para variables cualitativas. Se aplicó el test chi-cuadrado y el test ANOVA para evaluar la asociación de las respuestas con las variables: sexo, tipo de trabajador, área de trabajo y actividad en Unidades Covid-19. Resultados principales: Las enfermeras, médicos y auxiliares de enfermería trabajaban principalmente en áreas asistenciales y en unidades de alto riesgo de exposición. Los auxiliares de enfermería y las enfermeras tenían una mayor percepción de riesgo. Las enfermeras estaban menos implicadas en la organización, pero se sentían más apoyadas por sus compañeros. Los médicos se sentían más apoyados por sus superiores y mejor atendidos cuando tenían problemas de salud. Conclusión principal: Las enfermeras y auxiliares de enfermería presentaron mayor percepción de riesgo, las enfermeras se implicaron menos en la organización de la atención sanitaria, mientras que los médicos se sintieron más apoyados por sus superiores.(AU)

Objective: Healthcare professionals were the workers most affected by Covid-19, especially during the first waves of the pandemic. Thus, the aim of this study is to evaluate the perceived risk of exposure to Covid-19, the information received and the work participation between nurses, physicians and nursing assistants. Method: A cross-sectional study was conducted using an epidemiological survey among nurses, physicians and nursing assistants in a university hospital. Aspect and content validation, cognitive pretest, and piloting of the epidemiological survey was carried out with thirty subjects. A descriptive analysis was performed using mean and standard deviation (SD) for quantitative variables and absolute (n) and relative (%) frequencies for qualitative variables. The chi-square test and the ANOVA test were applied to assess the association of the responses with the variables: sex, type of worker, area of work and activity in Covid-19 Units. Results: Nurses, physicians and nursing assistants worked mainly in assistance areas and high risk of exposure units. Nursing assistants and nurses had a higher perception of risk. Nurses were less involved in the organization, but felt more supported by their colleagues. However, physicians felt more supported by their superiors and better care when they had a health problem. Conclusions: Nursing assistants and nurses presented higher risk perception, nurses were less involved in the organization of health care, while physicians felt more supported by their superiors.(AU)

[Risk perception, information received and occupational engagement of workers in a university hospital in the face of the COVID-19 pandemic.] / Percepción del riesgo, información recibida y participación laboral de los trabajadores de un hospital universitario ante la pandemia de la COVID-19.

OBJECTIVE: Hospital workers faced the pandemic with a lack of knowledge, procedures and resources, which generated different experiences based on the perceived risk of exposure. It was considered pertinent to conduct a study to learn about the risk perception, the information received and the occupational engagement of workers in a university hospital in the face of the pandemic. METHODS: A cross-sectional study (july-september 2020) was carried out by an ad hoc survey of workers in the Majadahonda Puerta de Hierro University Hospital with 20 items (Likert scale from 0=not at all agree to 5=totally agree). The sample size was set at 828 workers. The absolute frequency and percentage of agreement for each item were described. Chi-Square was used to assess the association of responses with sex, type of worker, work area and activity in COVID-19 units. RESULTS: 992 workers participated, with 80.7% being women, 79.8% healthcare personnel and 33.2% nurses. Workers perceived a high risk of exposure. Approximately half confirmed that they had received information on the use of masks, although not on PPE. More than half stated that they felt involved in teamwork, but not in COVID-19 unit planning. Statistically significant differences (p<0.05) were found in the risk perception by sex, between type of worker (healthcare vs. non-healthcare), work area (healthcare vs. non-healthcare) and working in COVID-19 Units vs. non-COVID-19 Units. CONCLUSIONS: Healthcare personnel who worked in care areas and COVID-19 units present greater perception of the risk of exposure, although they report a higher degree of agreement in the information received and in their work engagement in the face of the pandemic.

OBJETIVO: Los trabajadores del hospital afrontaron la pandemia con falta de conocimientos, procedimientos y recursos, lo que generó diferentes experiencias en base al riesgo de exposición percibido. Se consideró pertinente realizar un estudio para conocer la percepción del riesgo, la información recibida y la participación laboral de los trabajadores de un hospital universitario ante la pandemia. METODOS: Se realizó un estudio transversal (entre julio y septiembre de 2020) mediante una encuesta ad hoc con 20 ítems (Escala Likert de 0=nada de acuerdo a 5=totalmente de acuerdo) a los trabajadores del Hospital Universitario Puerta de Hierro Majadahonda, que desarrollaron su actividad laboral durante la primera ola pandémica de la COVID-19. El tamaño muestral se estableció en 828 sujetos. Se describieron la frecuencia absoluta y el porcentaje de acuerdo de cada ítem. Se usó la chi-cuadrado para valorar la asociación de las respuestas con el sexo, el tipo de trabajador, el área de trabajo y la actividad en unidades de COVID-19. RESULTADOS: Participaron 992 trabajadores, habiendo un 80,7% de mujeres, un de 79,8% personal sanitario y un 33,2% de enfermeras. Los trabajadores percibieron un alto riesgo de exposición. Aproximadamente la mitad afirmaron haber recibido información sobre el uso de mascarillas, aunque no de los equipos de protección individual (EPI). Más de la mitad afirmó sentirse partícipe del trabajo en equipo, pero no de la planificación de unidades de COVID-19. Se encontraron diferencias estadísticamente significativas (<0,05) en la percepción del riesgo por sexo, entre el tipo de trabajador (sanitario frente a no sanitario), el área de trabajo (asistencial frente a no asistencial) y trabajar en Unidades de COVID-19 frente a Unidades de no COVID-19. CONCLUSIONES: Los sanitarios que trabajaron en áreas asistenciales y unidades de COVID-19 presentan mayor percepción del riesgo de exposición, aunque refieren mayor grado de acuerdo en la información recibida y en su participación laboral ante la pandemia.

Percepción del riesgo, información recibida y participación laboral de los trabajadores de un hospital universitario ante la pandemia de la COVID-19 / Risk perception, information received and occupational engagement of workers in a university hospital in the face of the COVID-19 pandemic

FUNDAMENTOS: Los trabajadores del hospital afrontaron la pandemia con falta de conocimientos, procedimientos y recursos, lo que generó diferentes experiencias en base al riesgo de exposición percibido. Se consideró pertinente realizar un estudio para conocer la percepción del riesgo, la información recibida y la participación laboral de los trabajadores de un hospital universitario ante la pandemia. MÉTODOS: Se realizó un estudio transversal (entre julio y septiembre de 2020) mediante una encuesta ad hoc con 20 ítems (Escala Likert de 0=nada de acuerdo a 5=totalmente de acuerdo) a los trabajadores del Hospital Universitario Puerta de Hierro Majadahonda, que desarrollaron su actividad laboral durante la primera ola pandémica de la COVID-19. El tamaño muestral se estableció en 828 sujetos. Se describieron la frecuencia absoluta y el porcentaje de acuerdo de cada ítem. Se usó la chi-cuadrado para valorar la asociación de las respuestas con el sexo, el tipo de trabajador, el área de trabajo y la actividad en unidades de COVID-19.RESULTADOS: Participaron 992 trabajadores, habiendo un 80,7% de mujeres, un de 79,8% personal sanitario y un 33,2% de enfermeras. Los trabajadores percibieron un alto riesgo de exposición. Aproximadamente la mitad afirmaron haber recibido información sobre el uso de mascarillas, aunque no de los equipos de protección individual (EPI). Más de la mitad afirmó sentirse partícipe del trabajo en equipo, pero no de la planificación de unidades de COVID-19. Se encontraron diferencias estadísticamente significativas (p<0,05) en la percepción del riesgo por sexo, entre el tipo de trabajador (sanitario frente a no sanitario), el área de trabajo (asistencial frente a no asistencial) y trabajar en Unidades de COVID-19 frente a Unidades de no COVID-19.(AU)

BACKGROUND: Hospital workers faced the pandemic with a lack of knowledge, procedures and resources, which generated different experiences based on the perceived risk of exposure. It was considered pertinent to conduct a study to learn about the risk perception, the information received and the occupational engagement of workers in a university hospital in the face of the pandemic. METHODS: A cross-sectional study (july-september 2020) was carried out by an ad hoc survey of workers in the Majadahonda Puerta de Hierro University Hospital with 20 items (Likert scale from 0=not at all agree to 5=totally agree). The sample size was set at 828 workers. The absolute frequency and percentage of agreement for each item were described. Chi-Square was used to assess the associationof responses with sex, type of worker, work area and activity in COVID-19 units.RESULTS: 992 workers participated, with 80.7% being women, 79.8% healthcare personnel and 33.2% nurses. Workers perceived a high risk of exposure. Approximately half confirmed that they had received information on the use of masks, although not on PPE. More than half stated that they felt involved in teamwork, but not in COVID-19 unit planning. Statistically significant differences(p<0.05) were found in the risk perception by sex, between type of worker (healthcare vs. non-healthcare), work area (healthcare vs. non-healthcare) and working in COVID-19 Units vs. non-COVID-19 Units.CONCLUSIONS: Healthcare personnel who worked in care areas and COVID-19 units present greater perception of the risk of exposure, although they report a higher degree of agreement in the information received and in their work engagement in the face of the pandemic.(AU)

Effects of selective serotonin reuptake inhibitors and other antidepressant drugs on the risk of hip fracture: a case-control study in an elderly Mediterranean population.

OBJECTIVES: To describe the association between exposure to different antidepressant drugs and hip fracture in an elderly Mediterranean population. METHODS: Cases were all patients aged 50-95 years admitted to the emergency room of our hospital with hip fracture not related to a high intensity trauma during 2010. For each case, four controls were identified from primary care electronic medical records matched by age (±3 years), gender, date of consultation at the primary care centre (±1 month) and primary care centre. Pharmacological treatments received within the previous 5 years were retrieved from the prescription records. Crude and adjusted risks associated with exposures were calculated by conditional logistic regression. ORs were adjusted by matching variables and by significant risk factors identified in the bivariate analysis (prescription of ≥4 drugs, osteoporosis, diabetes mellitus and previous fracture). RESULTS: 136 cases and 544 controls were analysed. Adjusted OR (95% CI) for hip fracture associated with exposure to any antidepressants was 2.42 (1.24 to 4.73); for selective serotonin reuptake inhibitors (SSRIs) it was 3.52 (1.67 to 7.41), for non-selective monoamine reuptake inhibitors 1.07 (0.18 to 6.46) and for other antidepressants 0.82 (0.27 to 2.48). Sertraline (OR 3.88 (1.15 to 13.09)) was the only active principle with significant adjusted risk. When only exposures >6 months were considered, significant risks persisted for SSRIs (OR 2.64 (1.10 to 6.37)). CONCLUSIONS: The results of this study are coincident with other studies in which SSRIs, but not other types of antidepressants, are associated with an increased risk of hip fracture in our setting.

Study of the strength of the evidence and the redundancy of the research on pharmacological treatment for Alzheimer's disease: a cumulative meta-analysis and trial sequential analysis.

PURPOSE: To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to determine the number of redundant post-authorisation trials. METHODS: A cumulative meta-analysis with a trial sequential analysis (TSA) was performed. Primary outcomes were cognitive function assessed with ADAS-cog or SIB scales, discontinuation due to adverse events (AE) and discontinuation for any reason. The redundancy of post-authorisation clinical trials was studied by determining the novel aspects of each study on patient, intervention, comparator and trial outcome characteristics. Two criteria of futile trial (lenient and strict) were used. RESULTS: A total of 63 randomised clinical trials (RCTs) (16,576 patients) were included. It was conclusive that neither ChEI nor memantine achieved clinically significant improvement in cognitive function. In relation to safety, there was sufficient evidence to conclude that donepezil caused a clinically relevant increase on dropouts due to AE whereas the evidence was inconclusive for the remaining interventions. Regarding acceptability, it was conclusive that no ChEI improved treatment discontinuation while it was uncertain for memantine. The proportion of redundant trials was 5.6% with the lenient criteria and 42.6% with the strict one. CONCLUSIONS: The evidence is conclusive that ChEI and memantine do not achieve clinically significant symptomatic improvement in AD while the acceptability of ChEI is unsatisfactory. Although evidence on the safety of pharmacological interventions for AD and acceptability of memantine is inconclusive, no further RCTs are needed as their efficacy is not clinically relevant. Redundant trials were identified but their number depends on the criteria of futility used.

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

BACKGROUND: The risk-benefit relationship of memantine treatment for Alzheimer's disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates. METHODS: A systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials. RESULTS: Eighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE. CONCLUSIONS: Our study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship. PROSPERO REGISTRATION: CRD42014015696 .

Measuring anticholinergic exposure in patients with dementia: A comparative study of nine anticholinergic risk scales.

OBJECTIVE: To describe the prevalence and concordance of anticholinergic exposure according to 9 published scales, to quantify the relative weight of the drug subtypes included in each scale, and to identify clinical variables related to anticholinergic exposure. METHODS: Observational and cross-sectional study using 5323 cases of dementia diagnosed in the 7 hospitals of the public health care system of the Health Region of Girona (Spain) between 2007 and 2014 and registered by the Registry of Dementias of Girona (ReDeGi). We used the Pharmacy database that includes all the drugs prescribed by specialist and primary care physicians and dispensed in pharmacies. We calculated the anticholinergic exposure using the scoring rules of each scale. Age, gender, place of residence, dementia subtype, Clinical Dementia Rating score, Mini-Mental Status Examination score, and Blessed Dementia Rating Score at the moment of dementia diagnose were retrieved from the ReDeGi. RESULTS: Prevalence of the annual anticholinergic exposure ranged from 36.3% to 69.0% according to the different scales, the concordance among scales was poor to moderate, and the central nervous system drugs accounted the most for anticholinergic exposure. Being in a nursing home, having depressive symptoms, having a non-Alzheimer's dementia subtype, the number of drug treatments, and the severity of dementia were main determinants of anticholinergic exposure. CONCLUSIONS: There is a large difference in outcomes among the 9 anticholinergic risk scales. Clinicians and researchers should be aware of these differences when using these instruments in patients with dementia.

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.

Background: We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer's disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.

Effectiveness and safety of drugs used for stroke prevention in a cohort of non-valvular atrial fibrillation patients from a primary care electronic database.

PURPOSE: The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions. METHODS: We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes. RESULTS: We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADS2 ≥ 2, HR 0.65 (95%CI, 0.49-0.86), and CHA2 DS2 -VASc ≥ 2, HR 0.66 (95%CI, 0.52-0.84). We observed a higher risk of digestive bleeding with antiplatelets, HR 1.32 (95%CI, 1.01-1.73). Both VKA and antiplatelets were associated with reduction of all-cause mortality risk; HR 0.55 (95%CI, 0.49-0.62) and HR 0.89 (95%CI, 0.80-0.97), respectively. CONCLUSIONS: This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Psychostimulant drugs for cocaine dependence.

BACKGROUND: Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES: To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy. SEARCH METHODS: This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field. SELECTION CRITERIA: We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants and placebo (RD 0.00, 95% CI -0.01 to 0.01; RD 0.00, 95% CI -0.02 to 0.01, respectively). When we included the type of drug as a moderating variable, the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dexamphetamine than with placebo. Psychostimulants also appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone-maintained, dual heroin-cocaine addicts. Retention to treatment was low, though, so our results may be compromised by attrition bias. We found no evidence of publication bias. AUTHORS' CONCLUSIONS: This review found mixed results. Psychostimulants improved cocaine abstinence compared to placebo in some analyses but did not improve treatment retention. Since treatment dropout was high, we cannot rule out the possibility that these results were influenced by attrition bias. Existing evidence does not clearly demonstrate the efficacy of any pharmacological treatment for cocaine dependence, but substitution treatment with psychostimulants appears promising and deserves further investigation.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

Drug Therapy for Rate and Rhythm Control in Nonvalvular Atrial Fibrillation: A Cross-sectional Study With Electronic Health Records in a Primary Care Cohort.

PURPOSE: The purpose of this study is to describe the pharmacologic management of rate and rhythm and assess which factors are associated with the prescription of these drugs in patients with nonvalvular atrial fibrillation (AF) from the Effectiveness, Safety, and Costs in Atrial Fibrillation study. METHODS: This retrospective, cross-sectional study describes the pharmacologic rate and rhythm control management strategies adopted during 2012 in all patients diagnosed as having nonvalvular AF in 2007 to 2011. The data source is the Information System for the Improvement of Research in Primary Care database, which is based on primary care electronic health records. To answer the study objectives, 3 multivariate regression models to assess the independent factors associated with the prescription of these drugs were conducted for 2012. The rate and rhythm control drugs assessed were ß-blockers, nondihydropyridine calcium channel blockers, antiarrhythmic agents, and digoxin. FINDINGS: A total of 21,304 patients were diagnosed as having nonvalvular AF; 11,638 (54.6%) had at least one heart rate measure during 2012. Of them, 7777 (66.8%) received one or more rate and/or rhythm control drugs during 2012. Most patients (5751 [73.9%] of 7777) received only one drug for rate and/or rhythm control. Rate control agents were the most frequently used in 2012, with ß-blockers the most prescribed group (4091 patients [52.6%]). A variety of different variables were associated with the prescription of rate and/or rhythm control drugs in the multivariate regression models. IMPLICATIONS: The most used pharmacologic treatment of rate and rhythm control in our AF population is ß-blockers, indicating that a rate control strategy is preferred in our setting, as widely recommended.

Effectiveness, safety and costs of thromboembolic prevention in patients with non-valvular atrial fibrillation: phase I ESC-FA protocol study and baseline characteristics of a cohort from a primary care electronic database.

PURPOSE: Atrial fibrillation is the most common arrhythmia. Its management aims to reduce symptoms and to prevent complications through rate and rhythm control, management of concomitant cardiac diseases and prevention of related complications, mainly stroke. The main objective of Effectiveness, Safety and Costs in Atrial Fibrillation (ESC-FA) study is to analyse the drugs used for the management of the disease in real-use conditions, particularly the antithrombotic agents for stroke prevention. The aim of this work is to present the study protocol of phase I of the ESC-FA study and the baseline characteristics of newly diagnosed patients with atrial fibrillation in Catalonia, Spain. PARTICIPANTS: The data source is System for the Improvement of Research in Primary Care (SIDIAP) database. The population included are all patients with non-valvular atrial fibrillation diagnosis registered in the electronic health records during 2007-2012. FINDINGS TO DATE: A total of 22,585 patients with non-valvular atrial fibrillation were included in the baseline description. Their mean age was 72.8 years and 51.6% were men. The most commonly prescribed antithrombotics were vitamin K antagonists (40.1% of patients) and platelet aggregation inhibitors (32.9%); 25.3% had not been prescribed antithrombotic treatment. Age, gender, comorbidities and co-medication at baseline were similar to those reported for previous studies. FUTURE PLANS: The next phase in the ESC-FA study will involve assessing the effectiveness and safety of antithrombotic treatments, analysing stroke events and bleeding episodes' rates in our patients (rest of phase I), describing the current management of the disease and its costs in our setting, and assessing how the introduction of new oral anticoagulants changes the stroke prevention in non-valvular atrial fibrillation.

[Teaching Bioethics to Students of Medicine with Problem-Based Learning (PBL)]. / Enseñar Bioética a Estudiantes de Medicina Mediante el Aprendizaje Basado en Problemas (ABP).

We present the experience of the introduction of the subject of bioethics in a medical school in order to give to the 73 students of 5th degree skills to handle ethical conflicts in their practice. The main teaching method used was problem-based learning (PBL). Skills objectives are described. The course was structured with a theoretical seminar (2 hours of duration), a workshop (2 hours of duration), 4 cases of PBL (24 hours of duration in total) and a role playing workshop (2 hours of duration). The seminar was aimed at the acquisition of theoretical knowledge. The PBL cases provided critical appraisal, obtaining knowledge, and application. The Role Playing set out for the practical demonstration of skills acquired in a simulated environment. A continuous assessment of students was performed throughout their practice on the PBL cases (40% of the final score) and also a final evaluation of the course was carried out via exam (60% of the final score). Students completed a course and faculty evaluation anonymously, which came out with positive results (median score of 8.5/10).

Enseñar bioética a estudiantes de medicina mediante el aprendizaje basado en problemas (ABP) / Teaching bioethics to students of medicine with problema-based learning (PBL)

Se describe la implantación de la asignatura de Bioética en una Facultad de Medicina con el objetivo de dotar a los 73 alumnos de quinto curso de competencias para manejar conflictos éticos en su práctica profesional. El método docente utilizado principalmente fue el aprendizaje basado en problemas. Se describen las competencias y objetivos docentes marcados. El diseño de la asignatura consistió en un seminario teórico (2 horas), un taller práctico (2 horas), cuatro casos de aprendizaje basado en problemas (ABP) (24 horas en total) y un taller de dramatizaciones (Role Playing) (2 horas). El seminario se orientó a la adquisición de conocimientos teóricos básicos sobre bioética. Los casos ABP facilitaron la valoración crítica, la obtención de conocimiento, y su aplicación. Los Role Playing se encaminaron a la demostración práctica de las competencias adquiridas en un entorno simulado. Se realizó una evaluación continuada de los alumnos durante su trabajo en los casos ABP (40% de la nota), y una evaluación final de la asignatura mediante un examen (60% de la nota). Los alumnos evaluaron la asignatura y al profesorado de forma anónima, siendo los resultados positivos (8,5/10)

We present the experience of the introduction of the subject of bioethics in a medical school in order to give to the 73 students of 5th degree skills to handle ethical conflicts in their practice. The main teaching method used was problem-based learning (PBL). Skills objectives are described. The course was structured with a theoretical seminar (2 hours of duration), a workshop (2 hours of duration), 4 cases of PBL (24 hours of duration in total) and a role playing workshop (2 hours of duration). The seminar was aimed at the acquisition of theoretical knowledge. The PBL cases provided critical appraisal, obtaining knowledge, and application. The Role Playing set out for the practical demonstration of skills acquired in a simulated environment. A continuous assessment of students was performed throughout their practice on the PBL cases (40% of the final score) and also a final evaluation of the course was carried out via exam (60% of the final score). Students completed a course and faculty evaluation anonymously, which came out with positive results (median score of 8.5/10)

Frequency of ambulatory care adverse events in Latin American countries: the AMBEAS/PAHO cohort study.

OBJECTIVE: Determine the frequency and preventability of adverse events (AEs) from available information sources in selected ambulatory care (AC) sites in Latin America (LA). DESIGN: Multinational observational cohort was conducted to determine the period prevalence (retrospective focus) and the cumulative incidence (prospective focus) of AEs. SETTING: Outpatient clinics in Mexico, Peru, Brazil and Colombia. PARTICIPANTS: A random selection of 2080 patients. INTERVENTIONS: The existence of AE was decided based on trigger information provided by the patient and crossing the data with each patient's medical history. MAIN OUTCOME MEASURES: AE occurrences 6 months prior (prevalence) and 42 days after (incidence) the patient receiving AC were identified. AE type and preventability were also described. RESULTS: Two thousand eighty patients participated in the study. AEs prevalence was 5.2% (108/2080) [95% confidence interval (CI) 4.2-6.1%], and cumulative incidence was 2.4% (42/1757) (95% CI 1.7-3.1%). AEs considered preventable were 44% (55/108) of prevalence period, and 52.4% (22/42) of incidence period. Preventability was associated with patient socioeconomic status (OR 3.5, 95% CI 1.4-8.8), medication error (OR 0.1, 95% CI 0.0-0.4), diagnostic error (OR 0.1, 95% CI 0.0-0.8) and a minor impact on the patient (OR 0.2 95% CI 0.1-0.9). CONCLUSION: The frequency of AE in ambulatory settings in LA is in the high-frequency range of research focused on the prevalence of AEs. Fifty percent was preventable. This study provides an approach for assessing the frequency and preventability of AE in order to enhance patient safety in LA.

Efficacy of psychostimulant drugs for amphetamine abuse or dependence.

BACKGROUND: Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has been approved for this disorder, and psychotherapy remains the mainstay of treatment. In recent years, psychostimulants have been investigated as a possible replacement therapy. OBJECTIVES: To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence. The influences of type of drug, type of dependence, comorbid disorders, clinical trial risk of bias and publication of data were also studied. SEARCH METHODS: Relevant trials were searched in the following sources: PubMed (January 1966 to 6 June 2012), EMBASE (January 1988 to 6 June 2012), CENTRAL (The Cochrane Library, Issue 5 of 12, May 2012), PsycINFO (January 1985 to 6 June 2012) and the Specialised Register of the Cochrane Drug and Alcohol Group (June 2012). We also searched the reference lists of retrieved trials, the list of studies citing the included trials and the main electronic registers of ongoing trials (ClinicalTrials.gov, International Clinical Trials Registry Platform and EU Clinical Trials Register). Finally, we contacted investigators to request information about unpublished trials. Searches included non-English language literature. SELECTION CRITERIA: All randomised, placebo-controlled, parallel-group clinical trials investigating the efficacy or safety of psychostimulants for amphetamine dependence or abuse conducted in an outpatient setting. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI) -0.85 to 0.33) or amphetamine craving (MD 0.07, 95% CI -0.44 to 0.59) and did not increase sustained abstinence (relative risk (RR) 1.12, 95% CI 0.84 to 1.49). The proportion of adverse events inducing dropout was similar for psychostimulants and placebo (risk difference (RD) 0.01, 95% CI -0.03 to 0.04). The main findings did not change in any subgroup analysis. AUTHORS' CONCLUSIONS: Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy for amphetamine abuse or dependence. Future research could change this conclusion, as the numbers of included studies and participants are limited and information on relevant outcomes, such as efficacy according to the severity of dependence or craving, is still missing.