Non-specific protection against severe COVID-19 associated to typhoid fever and DTP vaccination.

Trained immunity (TRAIM) or the enhanced non-specific immune response after primary stimulation by infection or vaccination is a recent but well-recognized concept. To verify its predictions, our objective was to determine the effects of two bacterial vaccines, typhoid fever (TFV) and diphtheria-tetanus-pertussis (DTP) on the infection, hospitalization and death frequencies associated to COVID-19 in a retrospective study on subjects vaccinated or not with TFV and DTP in the 4 years prior to the start of COVID-19 pandemia in the Basque Country (Spain). The studied outcome records were split into two periods according to COVID-19 vaccination, the pre-vaccination (ACV) from March to December 2020 and the post-vaccination (PCV) from September 2021 to June 2022). In total, 13,673 subjects were vaccinated against TFV and 42,997 against DTP. A total of 2,005,084 individual records were studied in the ACV period and 1,436,693 in the PCV period. The proportion of infection, hospitalization and death associated to COVID-19 among controls in ACV was 4.97 %, 7.14 % and 3.54 %, respectively vs. 7.20 %, 2.24 % and 0.10 % among TFV subjects. Regarding DTP, the proportions were 4.97 %, 7.12 % and 3.58 % for controls and 5.79 %, 5.79 % and 0.80 % for vaccinees. In the PCV period, the proportion of infection, hospitalization and death among controls was 21.89 %, 2.62 % and 0.92 %, respectively vs. 31.19 %, 0.76 %, 0.00 % among TFV. For DTP, infection, hospitalization and death proportions were 21.89 %, 2.62 % and 0.92 %, respectively, among controls vs. 32.03 %, 1.85 % and 0.24 % among vaccinated subjects. The corresponding combined ACV and PCV odds ratios (OR) for SARS-CoV2 infection were 1.505 (95%CI 1.455-1.558; p < 0.0001; reduction -41.85 %) and 1.633 (95%CI 1.603-1.662; p < 0.0001; reduction -51.74 %), for TFV and DTP, respectively. Regarding COVID-19 associated hospitalization, the OR were 0.295 (95%CI 0.220-0.396; p = 0.0001; reduction 69.74 %) and 0.667 (95%CI 0.601-0.741; p = 0.0001; reduction 32.44 %), for TFV and DTP, respectively). COVID-19 associated death OR were 0.016 (95%CI 0.002-0.113, p < 0.0001; reduction 98.38 %) and 0.212 (95%CI 0.161-0.280; p = 0.0001; reduction 78.52 %), for TFV and DTP, respectively. We conclude that TRAIM effects by TFV and DTP vaccination in the four years prior to the pandemic SARS-CoV2 were supported by slightly increased infection rates, but strongly reduced COVID-19 associated hospitalization and death rates.

De-imFAR phase II project: a study protocol for a cluster randomised implementation trial to evaluate the effectiveness of de-implementation strategies to reduce low-value statin prescribing in the primary prevention of cardiovascular disease.

INTRODUCTION: This study aims to reduce potentially inappropriate prescribing (PIP) of statins and foster healthy lifestyle promotion in cardiovascular disease (CVD) primary prevention in low-risk patients. To this end, we will compare the effectiveness and feasibility of several de-implementation strategies developed following the structured design process of the Behaviour Change Wheel targeting key determinants of the clinical decision-making process in CVD prevention. METHODS AND ANALYSIS: A cluster randomised implementation trial, with an additional control group, will be launched, involving family physicians (FPs) from 13 Integrated Healthcare Organisations (IHOs) of Osakidetza-Basque Health Service with non-zero incidence rates of PIP of statins in 2021. All FPs will be exposed to a non-reflective decision assistance strategy based on reminders and decision support tools. Additionally, FPs from two of the IHOs will be randomly assigned to one of two increasingly intensive de-implementation strategies: adding a decision information strategy based on knowledge dissemination and a reflective decision structure strategy through audit/feedback. The target population comprises women aged 45-74 years and men aged 40-74 years with moderately elevated cholesterol levels but no diagnosed CVD and low cardiovascular risk (REGICOR<7.5%), who attend at least one appointment with any of the participating FPs (May 2022-May 2023), and will be followed until May 2024. We use the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate outcomes. The main outcome will be the change in the incidence rate of PIP of statins and healthy lifestyle counselling in the study population 12 and 24 months after FPs' exposure to the strategies. Moreover, FPs' perception of their feasibility and acceptability, and patient experience regarding the quality of care received will be evaluated. ETHICS AND DISSEMINATION: The study was approved by the Basque Country Clinical Research Ethics Committee and was registered in ClinicalTrials.gov (NCT04022850). Results will be disseminated in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04022850.

Variables associated with COVID-19 severity: an observational study of non-paediatric confirmed cases from the general population of the Basque Country, Spain.

OBJECTIVES: To investigate which were the most relevant sociodemographic and clinical variables associated with COVID-19 severity, and uncover how their inter-relations may have affected such severity. DESIGN: A retrospective observational study based on electronic health record data. PARTICIPANTS: Individuals ≥14 years old with a positive PCR or serology test, between 28 February and 31 May 2020, belonging to the Basque Country (Spain) public health system. Institutionalised and individuals admitted to a hospital at home unit were excluded from the study. MAIN OUTCOME MEASURE: Three severity categories were established: primary care, hospital/intensive care unit admission and death. RESULTS: A total of n=14 197 cases fulfilled the inclusion criteria. Most variables presented statistically significant associations with the outcome (p<0.0001). The Classification and Regression Trees recursive partitioning methodology (based on n=13 792) suggested that among all associations, those with, age, sex, stratification of patient healthcare complexity, chronic consumption of blood and blood-forming organ, and nervous system drugs, as well as the total number of chronic Anatomical Therapeutic Chemical types were the most relevant. Psychosis also emerged as a potential factor. CONCLUSIONS: Older cases are more likely to experience more severe outcomes. However, the sex, underlying health status and chronic drug consumption may interfere and alter the ageing effect. Understanding the factors related to the outcome severity is of key importance when designing and promoting public health intervention plans for the COVID-19 pandemic.

Evaluación de una intervención formativa con revisión estructurada de la medicación en pacientes mayores polimedicados en Atención Primaria / Evaluation of an educational intervention and a structured review of polypharmacy in elderly patients in Primary Care

Antecedentes y objetivo: Diversas intervenciones han demostrado que reducen la polimedicación y la prescripción potencialmente inapropiada (PPI). El objetivo del estudio fue evaluar el número de fármacos y PPI antes y después de una intervención educativa sobre el médico de atención primaria (MAP), con identificación electrónica de la PPI y revisión estructurada de la medicación, en ancianos con polimedicación excesiva (≥10 fármacos). Material y métodos: Estudio de intervención antes-después, en la Comarca Guipúzcoa (Osakidetza), en una muestra aleatoria de mayores de 80 años con ≥10 fármacos, cuyos MAP recibieron formación. Variables principales: cambio en el número de fármacos y PPI, evaluados por historia clínica. Variables secundarias: descripción del balance beneficio-riesgo evaluado por el MAP, problemas de seguridad y decisión terapéutica. Resultados: De los 591 pacientes elegibles, se excluyó a 88 (41: sus MAP no asistieron a la formación, 47: fallecimiento/traslado/ingreso) y se incluyó a 503, con una edad media de 84,9 años; el 67,7% eran mujeres. El número medio de fármacos y de PPI por paciente disminuyó significativamente: −0,88 (IC 95%: −1,04 a −0,72) y −0,19 (IC 95%: −0,29 a −0,09), respectivamente (p<0,0001), con una reducción del 25,8% en el número de pacientes con polimedicación excesiva. Variables secundarias: se emplearon hojas de recogida de datos de 365 pacientes y de 4.168 prescripciones. El balance beneficio-riesgo fue favorable para el 75% de las prescripciones y la decisión terapéutica mayoritaria fue mantenerlas (83%). Se mantuvieron el 47,3% de las 911 prescripciones con balance desfavorable/incierto. Conclusiones: La intervención se asocia con una reducción en la polimedicación excesiva y de la PPI en condiciones de práctica clínica habitual

Background and objective: Several interventions have been shown to reduce polypharmacy and potentially inappropriate prescription (PIP). The objective of the study was to evaluate the number of drugs and PIP before and after an educational intervention with the Primary Care physician (PCP), with electronic identification of PIP and structured medication review, in elderly patients with excessive polypharmacy (≥10 drugs). Material and methods: A before-after intervention study was conducted in the Gipuzkoa district of Osakidetza (Basque Country Health System), in a random sample of patients older than 80 years taking ≥ 10 drugs, and whose PCP attended training sessions. Primary outcomes: change in the number of drugs and PIP, registered in computerised health records. Secondary outcomes: benefit/risk ratio assessed by the PCP, safety problems, and therapeutic decision. Results: Of the 591 eligible patients, 88 were excluded (41: PCP did not attend training sessions, 47: death/transfer/admission), including a total of 503 patients with mean age of 84.9 years, with 67.7% women. The mean number of drugs and PIP per patient decreased significantly, −0.88 (95% CI: −1.04 to −0.72) and −0.19 (95% CI: −0.29 to −0.09), respectively (p<.0001), with a 25.8% reduction in the number of patients with excessive polypharmacy. Secondary outcomes: data collection sheets of 365 patients and 4,168 prescriptions were collected. The benefit-risk ratio was favourable for 75% of the prescriptions, with the most frequent decision being to maintain them (83%). Among the 911 prescriptions with an unfavourable/uncertain benefit/risk ratio, 47.3% were maintained. Conclusions: The intervention is associated with a reduction in excessive polypharmacy and PPI under real-world conditions

[Evaluation of an educational intervention and a structured review of polypharmacy in elderly patients in Primary Care]. / Evaluación de una intervención formativa con revisión estructurada de la medicación en pacientes mayores polimedicados en Atención Primaria.

BACKGROUND AND OBJECTIVE: Several interventions have been shown to reduce polypharmacy and potentially inappropriate prescription (PIP). The objective of the study was to evaluate the number of drugs and PIP before and after an educational intervention with the Primary Care physician (PCP), with electronic identification of PIP and structured medication review, in elderly patients with excessive polypharmacy (≥10 drugs). MATERIAL AND METHODS: A before-after intervention study was conducted in the Gipuzkoa district of Osakidetza (Basque Country Health System), in a random sample of patients older than 80 years taking ≥ 10 drugs, and whose PCP attended training sessions. Primary outcomes: change in the number of drugs and PIP, registered in computerised health records. SECONDARY OUTCOMES: benefit/risk ratio assessed by the PCP, safety problems, and therapeutic decision. RESULTS: Of the 591 eligible patients, 88 were excluded (41: PCP did not attend training sessions, 47: death/transfer/admission), including a total of 503 patients with mean age of 84.9 years, with 67.7% women. The mean number of drugs and PIP per patient decreased significantly, -0.88 (95% CI: -1.04 to -0.72) and -0.19 (95% CI: -0.29 to -0.09), respectively (p<.0001), with a 25.8% reduction in the number of patients with excessive polypharmacy. SECONDARY OUTCOMES: data collection sheets of 365 patients and 4,168 prescriptions were collected. The benefit-risk ratio was favourable for 75% of the prescriptions, with the most frequent decision being to maintain them (83%). Among the 911 prescriptions with an unfavourable/uncertain benefit/risk ratio, 47.3% were maintained. CONCLUSIONS: The intervention is associated with a reduction in excessive polypharmacy and PPI under real-world conditions.

Results from the CLUES study: a cluster randomized trial for the evaluation of cardiovascular guideline implementation in primary care in Spain.

BACKGROUND: The implementation of evidence-based clinical practice guidelines (CPG) can improve patients care. To date, the impact of implementation strategies has not been evaluated in our context. This study is aimed to evaluate the effectiveness of a multifaceted tailored intervention targeting clinician education for the implementation of three cardiovascular risk-related CPGs (type 2 diabetes, hypertension and dyslipidemia) in primary care at the Basque Health Service compared with usual implementation. METHODS: We conducted a cluster randomized controlled trial in two urban districts with 43 primary care units (PCU). Data from all patients diagnosed with diabetes, hypertension and all those eligible for coronary risk (CR) assessment were included. In the control group, guidelines were introduced in the usual way (by email, intranet and clinical meetings). In the intervention group, the implementation also included a specific website and workshops. Primary endpoints were annual HbA1c testing (diabetes), annual general laboratory testing (hypertension) and annual CR assessment (dyslipidemia). Secondary endpoints were process, prescription and clinical endpoints related with guideline recommendations. Analysis was performed at a PCU level weighted by cluster size. RESULTS: Significant differences between groups were observed in primary outcomes in the dyslipidemia CPG: increased CR assessment for both women and men (weighted mean difference, WMD, 13.58 and 12.91%). No significant differences were observed in diabetes and hypertension CPGs primary outcomes. Regarding secondary endpoints, annual CR assessment was significantly higher in both diabetic and hypertensive patients in the intervention group (WMD 28.16 and 27.55%). Rates of CR assessment before starting new statin treatments also increased (WMD 23.09%), resulting in a lower rate of statin prescribing in low risk women. Diuretic prescribing was higher in the intervention group (WMD 20.59%). Clinical outcomes (HbA1c and blood pressure control) did not differ between groups. CONCLUSIONS: The multifaceted implementation proved to be effective to increase the CR assessment and to improve prescription, but ineffective to improve diabetes and hypertension related outcomes. In order to obtain real improvements when cardiovascular issues are tackled, perhaps other or additional interventions need to be implemented besides education of professionals. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN 88876909 (retrospectively registered on January 13, 2009).

Sistema GRADE: metodología para la realización de recomendaciones para la práctica clínica / GRADE: Methodology for formulating and grading recommendations in clinical practice

Las guías de práctica clínica proporcionan recomendaciones sobre los beneficios y desventajas de diferentes intervenciones disponibles en la asistencia sanitaria. Su adecuado desarrollo e implementación permitirían reducir la variabilidad en la práctica clínica, así como mejorar su calidad y su seguridad. El sistema GRADE es una herramienta que permite evaluar la calidad de la evidencia y graduar la fuerza de las recomendaciones en el contexto de desarrollo de guías de práctica clínica, revisiones sistemáticas o evaluación de tecnologías sanitarias. El objetivo de este artículo es describir las principales características del sistema GRADE a través de ejemplos relevantes en el contexto de la atención primaria

Clinical practice guidelines (CPG) provide recommendations on the benefits and harms of different healthcare interventions. Proper CPG development and implementation can potentially reduce variability in clinical practice while improving its quality and safety. The GRADE system is used to assess the quality of evidence and to grade the strength of recommendations in the context of the development of CPGs, systematic reviews or health technology assessments. The aim of this article is to describe the main characteristics of the GRADE system through relevant examples in the context of primary care

[GRADE: Methodology for formulating and grading recommendations in clinical practice]. / Sistema GRADE: metodología para la realización de recomendaciones para la práctica clínica.

Clinical practice guidelines (CPG) provide recommendations on the benefits and harms of different healthcare interventions. Proper CPG development and implementation can potentially reduce variability in clinical practice while improving its quality and safety. The GRADE system is used to assess the quality of evidence and to grade the strength of recommendations in the context of the development of CPGs, systematic reviews or health technology assessments. The aim of this article is to describe the main characteristics of the GRADE system through relevant examples in the context of primary care.

Attitudes and perceptions about clinical guidelines: a qualitative study with Spanish physicians.

BACKGROUND: Clinical guidelines (CGs) are popular for healthcare decision making but their acceptability and use by healthcare providers is influenced by numerous factors. Some of these factors are professional-related, such as knowledge and perceptions of and attitudes toward CGs in general. The aim of our study was to evaluate attitudes and perceptions of Spanish physicians towards CGs. METHODS: We coordinated six discussion groups with a total of 46 physicians. The participants were drawn from 12 medical specialties from both specialized and primary care. We recorded the sessions and transcribed the content verbatim. We analyzed the data using an approach based on the grounded theory. RESULTS: We identified two main constructs that defined the physicians' perceptions towards guidelines: knowledge and usefulness. "Knowledge" defined the theoretical meanings of guidelines, while "Usefulness" referred to the pragmatic approach to guidelines. These constructs were interrelated through a series of categories such as confidence, usability, accessibility, dissemination and formats. CONCLUSIONS: In our study, the constructs that impacted most on physician's attitudes to clinical guidelines were knowledge and usefulness. The tension between the theoretical and the pragmatic constructs determined the attitudes and how physicians use guidelines. Groups developing guidelines should ask relevant clinical questions and develop implementable and context specific recommendations. Developers should be explicit and consistent in the development and presentation of recommendations.

The CLUES study: a cluster randomized clinical trial for the evaluation of cardiovascular guideline implementation in primary care.

BACKGROUND: The appropriate care for people with cardiovascular risk factors can reduce morbidity and mortality. One strategy for improving the care for these patients involves the implementation of evidence-based guidelines. To date, little research concerning the impact of such implementation strategies in our setting has been published. Aims. To evaluate the effectiveness of a multifaceted tailored intervention in the implementation of three cardiovascular risk-related guidelines (hypertension, type 2 diabetes and dyslipidemia) in primary care in the Basque Health Service compared with usual implementation. METHODS/DESIGN: A two-year cluster randomized clinical trial in primary care in two districts in the Basque Health Service. All primary care units are randomized. Data from all patients with diabetes, hypertension and those susceptible to coronary risk screening will be analyzed.Interventions. The control group will receive standard implementation. The experimental group will receive a multifaceted tailored implementation strategy, including a specific web page and workshops for family physicians and nurses.Endpoints. Primary endpoints: annual request for glycosylated hemoglobin, basic laboratory tests for hypertension, cardiovascular risk screening (women between 45-74 and men between 40-74 years old). Secondary endpoints: other process and clinical guideline indicators. ANALYSIS: Data will be extracted from centralized computerized medical records. ANALYSIS will be performed at a primary care unit level weighted by cluster size. DISCUSSION: The main contribution of our study is that it seeks to identify an effective strategy for cardiovascular guideline implementation in primary care in our setting. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN88876909.

EBM in primary care: a qualitative multicenter study in Spain.

BACKGROUND: Evidence based medicine (EBM) has made a substantial impact on primary care in Spain over the last few years. However, little research has been done into family physicians (FPs)' attitudes related to EBM. The present study investigates FPs' perceptions of EBM in the primary care context. METHODS: This study used qualitative methodology. Information was obtained from 8 focus groups composed of 67 FPs from 47 health centers in 4 autonomous regions in Spain. Intentional sampling considered participants' previous education in EBM, and their experience as tutors in family medicine or working groups' members of the Spanish Society of Family Practice. Sociological discourse analysis was used with the support of the MAXqda software. Results were validated by means of triangulation among researchers and contrast with participants. RESULTS: Findings were grouped into three main areas: 1) The tug-of-war between the "science" of EBM and "experience" in the search for good clinical practice in primary care; 2) The development of EBM sensemaking as a reaction to contextual factors and interests; 3) The paradox of doubt and trust in the new EBM experts.The meaning of EBM was dynamically constructed within the primary care context. FPs did not consider good clinical practice was limited to the vision of science that EBM represents. Its use appeared to be conditioned by several factors that transcended the common concept of barriers. Along with concerns about its objectivity, participants showed a tendency to see EBM as the use of simplified guidelines developed by EBM experts. CONCLUSIONS: The identification of science with EBM and its recognition as a useful but insufficient tool for the good clinical practice requires rethinking new meanings of evidence within the primary care reality. Beyond the barriers related to accessing and putting into practice the EBM, its reactive use can determine FPs' questions and EBM development in a direction not always centred on patients' needs. The questioning of experts' authority as a pillar of EBM could be challenged by the emergence of new kinds of EBM texts and experts to believe in.

Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems: a protocol for a qualitative study and a national survey.

BACKGROUND: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. METHODS/DESIGN: A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. DISCUSSION: Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere.

Perceptions, attitudes and knowledge of evidence-based medicine in primary care in Spain: a study protocol.

BACKGROUND: The philosophy of evidence-based medicine (EBM) was introduced in the early 90s as a new approach to the practice of medicine, using the best available evidence to make decisions about health care. Despite ongoing controversy, EBM has developed enormously and physicians' attitude towards it is generally positive. Nevertheless, in Spain little is known about this topic. We will therefore undertake a study to explore perceptions, attitudes and knowledge about EBM among primary care physicians. METHODS AND DESIGN: A mixed-method study combining qualitative and quantitative designs will target family practitioners in Spain with the objective of evaluating current attitudes and perceptions about evidence-based medicine. The project will consist of two phases: a first phase running focus groups to identify perceptions and attitudes of participants, and a second phase assessing their attitudes and knowledge about EBM by means of a survey. Both phases will explore these issues in three different subgroups: family practitioners, with or without previous formal education in EBM; members of working groups that formulate healthcare recommendations; and physicians in charge of training family practice residents. Additionally, we will undertake a systematic review to identify and synthesize the available evidence on this topic. DISCUSSION: The study will identify and gain insight into the perceived problems and barriers to the practice of evidence-based medicine among general practitioners in Spain. The project will also evaluate the main knowledge gaps and training needs, and explore how evidence-based medicine is being taught to family medicine residents, the medical practitioners of the future. Our results will aid researchers and health care planners in developing strategies to improve the practice of evidence-based medicine in our country.

Gaining insight into the Clinical Practice Guideline development processes: qualitative study in a workshop to implement the GRADE proposal in Spain.

BACKGROUND: The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out. METHODS: Qualitative research with an ethnographic approach, through non-participant observation and focus groups within the context of a consensus workshop in which 19 CPG experts participated to evaluate the GRADE proposal using 12 evidence tables taken from hypertension, asthma and arthritis CPGs. The interventions were recorded, under a guarantee of confidentiality. The transcriptions and field notes were analyzed, based on a sociological discourse analysis model, and the provisional findings were re-sent to participants in order to improve their validity. RESULTS: 1) Certain problems over procedure and terminology hindered the acceptance of this new method as a common reference system for the preparation of CPGs. 2) A greater closeness to clinical practice was accompanied by concerns over value judgments and subjectivity, with a demand for greater explicitness in the consensus process. 3) The type of "evidence" on which the guidelines are based, how and by whom the evidence is prepared, and what the role of the different actors should be, all constitute unresolved concerns in the CPG preparation and implementation processes. 4) The grading process is not neutral: professional background, prior experience and the degree of leadership all condition the participants' input and interactions. CONCLUSION: The findings obtained allow the quantitative evaluation to be better interpreted and, in turn, go beyond the particularities of the GRADE method. Adaptation to the complexities of clinical practice, the need for carefully designed multi-disciplinary work and the reflexivity present in the CPG preparation process, all represent lines of debate that are necessary to improve the CPG quality in the Spanish health care sector.