Magnitude and determinants of antibiotic dispensing without prescription in Spain: a simulated patient study.

Objectives: Excessive and inappropriate use of antibiotics increases antimicrobial resistance. The aim of this study was to determine the magnitude and determinants of antibiotic dispensing without prescription in Spain by the simulated patient technique. Methods: A cross-sectional study was conducted with all the pharmacies in a region of north-west Spain (n = 977), between December 2016 and January 2017. Four actors visited the pharmacies simulating a respiratory infection. Four incremental levels of pressure were used to obtain an antibiotic. The education and sex of the person who was dispensing and the area where the pharmacy was located were recorded. The effect of these independent variables on the dispensing of an antibiotic without prescription (1 = yes, 0 = no) was modelled by logistic regression. Results: An antibiotic was obtained in 18.83% (95% CI = 16.5%-21.41%) of the visits. The area influenced the dispensing of antibiotics without a medical prescription, with a greater likelihood of dispensing in rural (OR = 1.79; 95% CI = 1.20-2.68) or semi-rural (OR = 1.66; 95% CI = 1.13-2.44) areas than in urban areas. No association was found with the sex or the training of the person who dispensed the antibiotic. In the pharmacies in urban areas, a lower level of pressure was needed to obtain the antibiotic. Conclusions: This study shows that one-fifth of the pharmacies still dispense antibiotics without prescription, especially under patient pressure. A rural setting has been identified as a risk factor for dispensing without prescription, so it must be taken into account for future interventions.

Development and validation of the knowledge and attitudes regarding antibiotics and resistance (KAAR-11) questionnaire for primary care physicians.

OBJECTIVES: The aim of this study was to develop a novel, self-administered questionnaire to identify primary-care physicians' knowledge and attitudes regarding antibiotics and resistance (KAAR). METHODS: The study population comprised primary care physicians. The study was conducted in five phases. Phase I consisted of a systematic review and qualitative focus-group study (n = 33 physicians), in which items were formulated so as to be measured on a continuous, visual analogue scale (VAS); in Phase II, content validation and face validity were evaluated by a panel of experts, which reformulated, added and deleted items; Phase III consisted of a pilot study on a population possessing similar characteristics (n = 15); in Phase IV, we analysed reliability by means of a test-retest study (n = 91) and calculated the intraclass correlation coefficients (ICCs); and in Phase V, we assessed construct validity by applying the known-groups technique, measuring the differences between contrasting groups of physicians formed according to antibiotic prescription quality indicators (group 1, n = 156 versus group 2, n = 191). RESULTS: Following Phases I and II, the questionnaire contained 16 knowledge and attitude items. Participants in the pilot study (Phase III) reported no difficulty. The test-retest study (Phase IV) showed that 11 of the 16 initial knowledge and attitude items yielded an ICC > 0.5, while analysis of known-groups validity (Phase V) showed that 13 of the 16 initial items which assessed knowledge and attitudes discriminated between physicians with good and bad indicators of antibiotics prescription. CONCLUSION: The final 11 item KAAR questionnaire appears to be valid, reliable and responsive.

Determinants of antibiotic dispensing without a medical prescription: a cross-sectional study in the north of Spain.

OBJECTIVES: Antibiotic resistance is a major public health concern and is greatly exacerbated by inappropriate antibiotic use at a community level. The aim of this study was to ascertain which attitudes of community pharmacists were related to inappropriate antibiotic dispensing. METHODS: We conducted a cross-sectional study of community pharmacists in a region situated in northern Spain (n = 393). Personal interviews were conducted using a self-administered questionnaire. The degree of agreement with each item of knowledge and attitude was measured using an unnumbered, horizontal visual analogue scale, with replies being scored from 0 (total disagreement) to 10 (total agreement). The data were analysed using logistic regression. RESULTS: Of the total of 286 pharmacists (72.8%) who completed the questionnaire, 185 (64.7%) acknowledged having undertaken dispensing of antibiotics without a medical prescription (DAwMP). Attitudes such as patient complacency, external responsibility, indifference and insufficient knowledge were shown to be related to DAwMP. In contrast, no association was found with any of the pharmacists' personal or professional traits. CONCLUSIONS: This study confirms that, albeit unlawful, DAwMP is a common practice in Spanish pharmacies. DAwMP was seen to be usually associated with some of the attitudes evaluated.

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

[Survival impact of previous statin therapy in patients hospitalized with COVID-19]. / Impacto del tratamiento previo con estatinas sobre la supervivencia de los pacientes hospitalizados con COVID-19.

INTRODUCTION: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. METHODS: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. RESULTS: We studied 1122 hospitalized patients with COVID-19, whose median age was 71years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95%CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95%CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95%CI: 0.28-0.73). CONCLUSIONS: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease.

Survival impact of previous statin therapy in patients hospitalized with COVID-19.

Introduction: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. Methods: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. Results: We studied 1122 hospitalized patients with COVID-19, whose median age was 71 years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95% CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95% CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95% CI: 0.28-0.73). Conclusions: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease.

Introducción: El tratamiento con estatinas podría presentar un efecto pronóstico beneficioso en pacientes con COVID-19, dadas sus propiedades inmunomoduladoras, antiinflamatorias y estabilizadoras de la placa de ateroma. Nuestro propósito fue analizar esta hipótesis tomando como base el registro de COVID-19 de un hospital universitario español. Métodos: Realizamos un estudio observacional y retrospectivo en el que se incluyeron los pacientes hospitalizados con COVID-19 diagnosticado mediante PCR entre marzo de 2020 y octubre de 2020 en un centro. Mediante regresión logística, diseñamos una puntuación de propensión para estimar la probabilidad de que un paciente recibiese tratamiento con estatinas antes del ingreso. Comparamos la supervivencia de los pacientes con y sin tratamiento con estatinas mediante la regresión de Cox ponderada por la inversa de la probabilidad de recibir el tratamiento (IPT). La mediana de seguimiento fue de 406 días. Resultados: Estudiamos 1.122 pacientes hospitalizados con COVID-19, cuya mediana de edad era de 71 años y de los cuales 488 (43,5%) eran mujeres. 451 (40,2%) pacientes recibían estatinas antes del ingreso. En el análisis de supervivencia ponderado por la IPT, el tratamiento previo con estatinas se asoció a una reducción significativa de la mortalidad (HR: 0,76; IC 95%: 0,59­0,97). El mayor beneficio del tratamiento previo con estatinas se observó en los subgrupos de pacientes con enfermedad arterial coronaria (HR: 0,32; IC 95%: 0,18­0,56) y enfermedad arterial extracardiaca (HR: 0,45; IC 95%: 0,28­0,73). Conclusiones: Nuestro estudio mostró una asociación significativa entre el tratamiento previo con estatinas y una menor mortalidad en pacientes hospitalizados con COVID-19. El beneficio pronóstico observado fue mayor en los pacientes con enfermedad aterosclerótica coronaria o extracardiaca previa.

Attitudes of primary care physicians to the prescribing of antibiotics and antimicrobial resistance: a qualitative study from Spain.

BACKGROUND AND OBJECTIVE: Resistance to antibiotics is a public health threat. A number of studies confirm the relationship between antibiotic use and the resistance rate. As a whole, physicians represent a large proportion of the health professionals involved in the use of this therapeutic group. Our study therefore sought to ascertain the opinions and attitudes of GPs in Spain with respect to antibiotics and resistance. METHODS: We used the focus group (FG) method, with each group comprising 4-12 primary care physicians and a moderator. Based on a previous systematic review, we drew up an agenda to be followed during the holding of the sessions. Group proceedings were recorded and the transcriptions then analysed separately by two researchers. RESULTS: Five FGs were formed, including a total of 33 physicians. The factors/attitudes that influenced the prescribing of antibiotics by GPs were fear, complacency, insufficient knowledge and external responsibility of the pharmaceutical industry, patients and over-the-counter antibiotics. The groups felt that antibiotic resistance was not a problem at a community level. CONCLUSIONS: Identification of attitudes/knowledge related with inappropriate antibiotic prescribing will enable specific interventions to be designed, with the aim of targeting these shortcomings to improve antibiotic use and help reduce resistance.

Impact of a multifaceted intervention to improve antibiotic prescribing: a pragmatic cluster-randomised controlled trial.

OBJECTIVES: This study sought to assess the effectiveness and return on investment (ROI) of a multifaceted intervention aimed at improving antibiotic prescribing for acute respiratory infections in primary care. DESIGN: Large-sized, two-arm, open-label, pragmatic, cluster-randomised controlled trial. SETTING: All primary care physicians working for the Spanish National Health Service (NHS) in Galicia (region in north-west Spain). PARTICIPANTS: The seven spatial clusters were distributed by unequal randomisation (3:4) of the intervention and control groups. A total of 1217 physicians (1.30 million patients) were recruited from intervention clusters and 1393 physicians (1.46 million patients) from control clusters. INTERVENTIONS: One-hour educational outreach visits tailored to training needs identified in a previous study; an online course integrated in practice accreditation; and a clinical decision support system. MAIN OUTCOME MEASURES: Changes in the ESAC (European Surveillance of Antimicrobial Consumption) quality indicators for outpatient antibiotic use. We used generalised linear mixed and conducted a ROI analysis to ascertain the overall cost savings. RESULTS: Median follow-up was 19 months. The adjusted effect on overall antibiotic prescribing attributable to the intervention was - 4.2% (95% CI: - 5.3% to - 3.2%), with this being more pronounced for penicillins - 6.5 (95% CI: - 7.9% to - 5.2%) and for the ratio of consumption of broad- to narrow-spectrum penicillins, cephalosporins, and macrolides - 9.0% (95% CI: - 14.0 to - 4.1%). The cost of the intervention was €87 per physician. Direct savings per physician attributable to the reduction in antibiotic prescriptions was €311 for the NHS and €573 for patient contributions, with an ROI of €2.57 and €5.59 respectively. CONCLUSIONS: Interventions designed on the basis of gaps in physicians' knowledge of and attitudes to misprescription can improve antibiotic prescribing and yield important direct cost savings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24158380 . Registered 5 February 2009.

[Ethics Committee experience during COVID-19 emergency. A brief report.] / Experiencia de un Comité de Ética de la Investigación durante la pandemia por COVID-19.

OBJECTIVE: The health crisis caused by COVID-19 required the prompt launch of research in order to generate scientific evidence pertaining to the new disease oriented to control its devastating effects and continuous spread. Therefore, it was essential to adapt the work flow of Research Ethics Committees, to prioritize and to accelerate the evaluation of projects related to this disease. METHODS: This work analyses the evaluation conducted by our Regional Ethics Committees during the initial period of the health emergency (between 13th March and 28th May 2020). RESULTS: 81 research projects were evaluated, 73 of them of regional scope (62 single-centre), 4 national and 4 international. 57 projects obtained a favourable opinion, 4 were withdrawn by the sponsors, 6 did not require ethics approval and 14 did not respond to the clarifications requested up to the date of the study's closure. CONCLUSIONS: The most important research procedures to be analysed in this context are those related to the methodology and informed consent process. It is also essential to address aspects related to the privacy of personal data, and to take into account the workload of the researchers. As an improvement proposal, we think that greater collaboration between the different research teams should be encourage to obtain more robust results.

OBJETIVO: La crisis sanitaria motivada por la COVID-19 hace necesaria la puesta en marcha, con celeridad, de investigaciones encaminadas a generar evidencias científicas que incidan en el control de sus devastadores efectos. Por ello, fue necesario realizar ajustes en la dinámica de trabajo de los Comités de Ética de la Investigación, así como priorizar y agilizar la evaluación de los proyectos relacionados con dicha enfermedad. Este trabajo pretendió analizar la actividad la actividad evaluadora del Comité de Ética de la Investigación con Medicamentos de Galicia (CEIm-G) durante dicho período de emergencia sanitaria. METODOS: Se evaluaron 81 proyectos de investigación, 73 de ellos de ámbito autonómico (62 unicéntricos), 4 nacionales y 4 internacionales. RESULTADOS: En 57 proyectos el dictamen fue favorable, 4 fueron retirados por los promotores, en 6 no procedía dictamen y 14 no respondieron a las aclaraciones solicitadas hasta la fecha del cierre del estudio. CONCLUSIONES: Las causas más frecuentes de solicitud de aclaraciones están relacionadas con la metodología y, a continuación, con la hoja de información al paciente y el consentimiento informado. También es imprescindible abordar los aspectos relacionados con la intimidad de los datos personales y las muestras, e igualmente tener en cuenta la carga de trabajo de los investigadores. Como propuesta de mejora, consideramos que se debe incidir en una mayor coordinación entre los diferentes equipos de investigación para tratar de obtener resultados más robustos.

Pharmaceutical companies information and antibiotic prescription patterns: A follow-up study in Spanish primary care.

OBJECTIVES: To assess the impact of sources of drug information on antibiotic prescribing patterns (quantity and quality) among primary care physicians. METHODS: We conducted a cohort study on primary care physicians who were actively engaged in medical practice in 2010 in a region in north-west Spain (Galicia), fulfilling inclusion criteria (n = 2100). As the independent variable, we took the perceived utility of 6 sources of information on antibiotics, as measured by the validated KAAR-11 questionnaire. As dependent variables, we used: (1) a quality indicator (appropriate quality, defined as any case where 6 of the 12 indicators proposed by the European Surveillance of Antimicrobial Consumption Network [ESAC-Net] were better than the mean values for Spain); and, (2) a quantity indicator (high prescribing), defined as any case where defined daily doses (DDD) per 1 000 inhabitants per day of antibacterials for systemic use were higher than the mean values for Spain. The adjusted odds ratio for a change in the interquartile range (IqOR) for each sources of information on antibiotics was calculated using Generalized Linear Mixed Models. RESULTS: The questionnaire response rate was 68%. Greater perceived utility of pharmaceutical sales representatives increases the risk of having high prescribing (1/IqOR = 2.50 [95%CI: 1.63-3.66]) and reduces the probability of having appropriate quality (1/IqOR = 2.28 [95%CI: 1.77-3.01]). Greater perceived utility of clinical guidelines increases the probability of having appropriate quality (1/IqOR = 1.25 [95%CI: 1.02-1.54]) and reduces the probability of high prescribing (1/IqOR = 1.25 [95%CI: 1.02-1.54]). CONCLUSIONS: Sources of information on antibiotics are an important determinant of the quantity and quality of antibiotic prescribing in primary care. Commercial sources of information influence prescribing negatively, and clinical guidelines are associated with better indicators.

Knowledge, attitudes, perceptions and habits towards antibiotics dispensed without medical prescription: a qualitative study of Spanish pharmacists.

OBJECTIVE: To investigate community pharmacists' knowledge, attitudes, perceptions and habits with regard to antibiotic dispensing without medical prescription in Spain. METHODS: A qualitative research using focus group method (FG) in Galicia (north-west Spain). FG sessions were conducted in the presence of a moderator. A topic script was developed to lead the discussions, which were audiorecorded to facilitate data interpretation and transcription. Proceedings were transcribed by an independent researcher and interpreted by two researchers working independently. We used the Grounded Theory approach. SETTING: Community pharmacies in Galicia, region Norwest of Spain. PARTICIPANTS: Thirty pharmacists agreed to participate in the study, and a total of five FG sessions were conducted with 2-11 pharmacists. We sought to ensure a high degree of heterogeneity in the composition of the groups to improve our study's external validity. Pharmacists' participation had no gender or age restrictions, and an effort was made to form FGs with pharmacists who were both owners and non-owners, provided in all cases that they were Official Colleges of Pharmacists-registered community pharmacists. For the purpose of conducting FG discussions, the basic methodological principle of allowing groups to attain their 'own structural identity' was applied. MAIN OUTCOME MEASUREMENTS: Community pharmacists' habits and knowledge with regard to antibiotics and identification of the attitudes and/or factors that influence antibiotic dispensing without medical prescription. RESULTS: Pharmacists attributed the problem of antibiotics dispensed without medical prescription and its relationship to antibiotic resistance to the following attitudes: external responsibility (doctors, dentists and the National Health Service (NHS)); acquiescence; indifference and lack of continuing education. CONCLUSIONS: Despite being a problem, antibiotic dispensing without a medical prescription is still a common practice in community pharmacies in Galicia, Spain. This practice is attributed to acquiescence, indifference and lack of continuing education. The problem of resistance was ascribed to external responsibility, including that of patients, physicians, dentists and the NHS.

Effect of Physicians' Attitudes and Knowledge on the Quality of Antibiotic Prescription: A Cohort Study.

Resistance increases with the use and abuse of antibiotics. Since physicians are primarily responsible for the decision to use antibiotics, ascertaining the attitudes and knowledge that underlie their prescribing habits is thus a prerequisite for improving prescription. Three-year follow-up cohort study (2008-2010) targeting primary-care physicians (n = 2100) in Galicia, a region in NW Spain. We used data obtained from a postal survey to assess knowledge and attitudes. A physician was deemed to have demonstrated Appropriate Quality Prescription of Antibiotics (dependent variable) in any case where half or more of the indicators proposed by the European Surveillance of Antimicrobial Consumption had values that were better than the reference values for Spain. The mail-questionnaire response rate was 68·0% (1428/2100). The adjusted increase in the interquartile OR of displaying good prescribing of antibiotics for each attitude was: 205% for fear ("When in doubt, it is better to ensure that a patient is cured of an infection by using a broad-spectrum antibiotic"; 95%CI: 125% to 321%); 119% for better knowledge ("Amoxicillin is useful for resolving most respiratory infections in primary care"; 95%CI: 67% to 193%); and 21% for complacency with patients' demands ("Antibiotics are often prescribed due to patients' demands"; 95%CI: 0% to 45%). Due to the fact that physicians' knowledge and attitudes are potentially modifiable, the implementation of purpose-designed educational interventions based on the attitudes identified may well serve to improve antibiotic prescription.

Misprescription of antibiotics in primary care: a critical systematic review of its determinants.

BACKGROUND: Antibiotic resistance is one of the principal public health problems worldwide. Currently, inappropriate use of antibiotics is regarded as the principal determinant of resistance, with most of these drugs being prescribed outside a hospital setting. This systematic review sought to identify the factors, attitudes and knowledge linked to misprescription of antibiotics. METHODS: A systematic review was conducted using the MEDLINE-PubMed and EMBASE databases. The selection criteria required that papers: (1) be published in English or Spanish; (2) designate their objective as that of addressing attitudes/knowledge or other factors related with the prescribing of antibiotics; and (3) use quality and/or quantity indicators to define misprescription. The following were excluded: any paper that used qualitative methodology and any paper that included descriptive analysis only. RESULTS: A total of 46 papers that met the inclusion criteria were included in the review. They were very heterogeneous and displayed major methodological limitations. Doctors' socio-demographic and personal factors did not appear to exert much influence. Complacency (fulfilling what professionals perceived as being patients'/parents' expectations) and, to a lesser extent, fear (fear of possible complications in the patient) were the attitudes associated with misprescription of antibiotics. CONCLUSIONS: Before designing interventions aimed at improving the prescription and use of antibiotics, studies are needed to identify precisely which factors influence prescribing.

Selective serotonin reuptake inhibitors and gastrointestinal bleeding: a case-control study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal (GI) bleeding. Given their worldwide use, even small risks account for a large number of cases. This study has been conducted with carefully collected information to further investigate the relationship between SSRIs and upper GI bleeding. METHODS: We conducted a case-control study in hospitals in Spain and in Italy. Cases were patients aged ≥18 years with a primary diagnosis of acute upper GI bleeding diagnosed by endoscopy; three controls were matched by sex, age, date of admission (within 3 months) and hospital among patients who were admitted for elective surgery for non-painful disorders. Exposures to SSRIs, other antidepressants and other drugs were defined as any use of these drugs in the 7 days before the day on which upper gastrointestinal bleeding started (index day). RESULTS: 581 cases of upper GI bleeding and 1358 controls were considered eligible for the study; no differences in age or sex distribution were observed between cases and controls after matching. Overall, 4.0% of the cases and 3.3% of controls used an SSRI antidepressant in the week before the index day. No significant risk of upper GI bleeding was encountered for SSRI antidepressants (adjusted odds ratio, 1.06, 95% CI, 0.57-1.96) or for whichever other grouping of antidepressants. CONCLUSIONS: The results of this case-control study showed no significant increase in upper GI bleeding with SSRIs and provide good evidence that the magnitude of any increase in risk is not greater than 2.