Antibiotic Prophylaxis to Reduce Respiratory Tract Infections and Mortality in Adults Receiving Intensive Care

BACKGROUND: Pneumonia is an important cause of mortality in intensive care units (ICUs). The incidence of pneumonia in ICU patients ranges between 7% and 40%, and the crude mortality from ventilator-associated pneumonia may exceed 50%. Although not all deaths in patients with this form of pneumonia are directly attributable to pneumonia, it has been shown to contribute to mortality in ICUs independently of other factors that are also strongly associated with such deaths. OBJECTIVES: To assess the effects of prophylactic antibiotic regimens, such as selective decontamination of the digestive tract (SDD) for the prevention of respiratory tract infections (RTIs) and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register; MEDLINE (January 1966 to March 2009); and EMBASE (January 1990 to March 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) of antibiotic prophylaxis for RTIs and deaths among adult ICU patients. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed trial quality. MAIN RESULTS: We included 36 trials involving 6914 people. There was variation in the antibiotics used, patient characteristics and risk of RTIs and mortality in the control groups. In trials comparing a combination of topical and systemic antibiotics, there was a significant reduction in both RTIs (number of studies = 16, odds ratio (OR) 0.28, 95% confidence interval (CI) 0.20 to 0.38) and total mortality (number of studies = 17, OR 0.75, 95% CI 0.65 to 0.87) in the treated group. In trials comparing topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) there was a significant reduction in RTIs (number of studies = 17, OR 0.44, 95% CI 0.31 to 0.63) but not in total mortality (number of studies = 19, OR 0.97, 95% CI 0.82 to 1.16) in the treated group. AUTHORS' CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics reduces RTIs and overall mortality in adult patients receiving intensive care. Treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect

Data extraction methods: an analysis of internal reporting discrepancies in single manuscripts and practical advice

Background: Data extraction from reports about experimental or observational studies is a crucial methodological step informing evidence syntheses, such as systematic reviews (SRs) and overviews of SRs. Reporting discrepancies were defined as pairs of statements that could not both be true. Authors of SRs and overviews of SRs can encounter reporting discrepancies among multiple sources when extracting data—a manuscript and a conference abstract, and a manuscript and a clinical trial registry. However, these discrepancies can also be found within a single manuscript published in a scientific journal. Objectives: Hereby, we describe examples of internal reporting discrepancies that can be found in a single source, with the aim of raising awareness among authors of SRs and overviews of SRs about such potential methodological issues. Conclusions: Authors of SRs and overviews of SRs should check whether the same information is reported in multiple places within a study and compare that information. Independent data extraction by two reviewers increases the chance of finding discrepancies, if they exist. We provide advice on how to deal with different types of discordances and how to report such discordances when conducting SRs and overviews of SRs

Characteristics and impact of interventions to support healthcare providers’ compliance with guideline recommendations for breast cancer: a systematic literature review

BackgroundBreast cancer clinical practice guidelines (CPGs) offer evidence-based recommendations to improve quality of healthcare for patients. Suboptimal compliance with breast cancer guideline recommendations remains frequent, and has been associated with a decreased survival. The aim of this systematic review was to characterize and determine the impact of available interventions to support healthcare providers' compliance with CPGs recommendations in breast cancer healthcare.MethodsWe searched for systematic reviews and primary studies in PubMed and Embase (from inception to May 2021). We included experimental and observational studies reporting on the use of interventions to support compliance with breast cancer CPGs. Eligibility assessment, data extraction and critical appraisal was conducted by one reviewer, and cross-checked by a second reviewer. Using the same approach, we synthesized the characteristics and the effects of the interventions by type of intervention (according to the EPOC taxonomy), and applied the GRADE framework to assess the certainty of evidence.ResultsWe identified 35 primary studies reporting on 24 different interventions. Most frequently described interventions consisted in computerized decision support systems (12 studies); educational interventions (seven), audit and feedback (two), and multifaceted interventions (nine). There is low quality evidence that educational interventions targeted to healthcare professionals may improve compliance with recommendations concerning breast cancer screening, diagnosis and treatment. There is moderate quality evidence that reminder systems for healthcare professionals improve compliance with recommendations concerning breast cancer screening. There is low quality evidence that multifaceted interventions may improve compliance with recommendations concerning breast cancer screening. The effectiveness of the remaining types of interventions identified have not been evaluated with appropriate study designs for such purpose. There is very limited data on the costs of implementing these interventions.ConclusionsDifferent types of interventions to support compliance with breast cancer CPGs recommendations are available, and most of them show positive effects. More robust trials are needed to strengthen the available evidence base concerning their efficacy. Gathering data on the costs of implementing the proposed interventions is needed to inform decisions about their widespread implementation

Healthcare providers' adherence to breast cancer guidelines in Europe : a systematic literature review

Clinical guidelines' (CGs) adherence supports high-quality care. However, healthcare providers do not always comply with CGs recommendations. This systematic literature review aims to assess the extent of healthcare providers' adherence to breast cancer CGs in Europe and to identify the factors that impact on healthcare providers' adherence. We searched for systematic reviews and quantitative or qualitative primary studies in MEDLINE and Embase up to May 2019. The eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and cross-checked by a second author. We conducted a narrative synthesis attending to the modality of the healthcare process, methods to measure adherence, the scope of the CGs, and population characteristics. Out of 8137 references, we included 41 primary studies conducted in eight European countries. Most followed a retrospective cohort design (19/41; 46%) and were at low or moderate risk of bias. Adherence for overall breast cancer care process (from diagnosis to follow-up) ranged from 54 to 69%; for overall treatment process [including surgery, chemotherapy (CT), endocrine therapy (ET), and radiotherapy (RT)] the median adherence was 57.5% (interquartile range (IQR) 38.8-67.3%), while for systemic therapy (CT and ET) it was 76% (IQR 68-77%). The median adherence for the processes assessed individually was higher, ranging from 74% (IQR 10-80%), for the follow-up, to 90% (IQR 87-92.5%) for ET. Internal factors that potentially impact on healthcare providers' adherence were their perceptions, preferences, lack of knowledge, or intentional decisions. A substantial proportion of breast cancer patients are not receiving CGs-recommended care. Healthcare providers' adherence to breast cancer CGs in Europe has room for improvement in almost all care processes. CGs development and implementation processes should address the main factors that influence healthcare providers' adherence, especially patient-related ones. Registration:: PROSPERO (CRD42018092884)

La produzione di raccomandazioni cliniche con il metodo GRADE: l'esperienza sui farmaci oncologici

Questo Dossier \ue8 dedicato alla presentazione del background scientifico e dei risultati del Progetto AFO (Appropriatezza farmaci oncologici) sviluppato dall\u2019Agenzia sanitaria e sociale della Regione Emilia-Romagna nell\u2019ambito del Programma Ricerca e innovazione (PRI E-R). Dal punto di vista del background scientifico l\u2019elemento di originalit\ue0 del progetto \ue8 stato la sperimentazione dell\u2019uso del metodo GRADE (Grading of Recommendations Assessment, Development and Evaluation) per la produzione e graduazione di raccomandazioni cliniche relative all\u2019effetto degli interventi sanitari. Il metodo GRADE \ue8 nato dall\u2019attivit\ue0 avviata nel 2000 di un gruppo di lavoro internazionale che ha ritenuto necessario mettere a punto un approccio unificato alla produzione di raccomandazioni cliniche in presenza di una molteplicit\ue0 di sistemi di grading tra loro non sempre coerenti e la cui variabilit\ue0 mette in serio pericolo la fruibilit\ue0 dello strumento linee guida/raccomandazioni. Dal punto di vista dei contenuti e delle modalit\ue0 operative, il Progetto AFO - che ha anche ottenuto un finanziamento da parte del Ministero del Lavoro, della salute e delle politiche sociali nell\u2019ambito del Programma Ricerca finalizzata (Fondo ex art. 12 DLgs 502/1992) - \ue8 nato con l\u2019obiettivo di sperimentare la possibilit\ue0 di coinvolgere gruppi multidisciplinari di clinici nella produzione di raccomandazioni sull\u2019uso appropriato di farmaci oncologici, sia nuovi sia gi\ue0 registrati ma in evoluzione per quanto riguarda le indicazioni cliniche. Nella prima parte del Dossier, dopo una breve introduzione relativa alla filosofia del programma PRI E-R e agli scopi del progetto AFO, viene presentato il metodo GRADE, le sue assunzioni e le tappe operative di applicazione. Nella seconda parte vengono presentati i risultati del lavoro dei tre panel multisciplinari che hanno prodotto complessivamente 32 raccomandazioni per la terapia adiuvante e la fase avanzata del trattamento dei tumori della mammella, del colon retto e del polmone. Conclude la seconda parte del Dossier una discussione circa le criticit\ue0 di applicazione del metodo e le potenzialit\ue0 e i limiti del suo utilizzo per la produzione di strumenti utili al miglioramento dell\u2019appropriatezza d\u2019uso dei farmaci. Nell\u2019Appendice viene infine riportato, a scopo esemplificativo, il testo di due raccomandazioni relative all\u2019uso del trastuzumab nella terapia adiuvante del tumore della mammella e delle fluoropirimidine nella terapia adiuvante del tumore del colon.This report is devoted to the presentation of the scientific background and results of the AFO (an acronym standing for Appropriateness of Oncologic Drugs) project developed by the Health Care and Social Agency of Emilia-Romagna region in the framework of the Research and Innovation program (PRI E-R). From the methodological standpoint the novelty of the project stems from the utilisation of the GRADE method (Grading of Recommendation, Assessment, Development and Evaluation) for the production and grading of clinical recommendations on the effects of health care interventions. The GRADE method originated from the work of an international working group that, starting 2001, was convened to go beyond the variations in the existing methods for producing and grading clinical recommendations. These variations were mostly due to conceptual inconsistencies that, if not properly recognised and addressed, would jeopardise the credibility of the entire guidelines movement. From the subject matter standpoint the AFO project - which was also partially supported by a research grant from the Italian Ministry of Welfare, Health and Social Affairs - was conceived to test the feasibility of a working methodology where multidisciplinary panels of clinicians would be convened to produce clinical recommendations on newly registered drugs as well as those already in widespread use but whose indications change over time. In the first part of the report, after a brief introduction on the working hypotheses and objectives of the PRI ER program and the AFO project, the GRADE method is presented and discussed. In the second part the results of the activities of the three panels that produced a total of 32 recommendations for the adjuvant and advanced treatment of breast, colorectal and lung cancer are reported. The final session of the report addresses some open issues relative to the application of the GRADE method to the production of clinical recommendations construed with the explicit aim of improving quality and appropriateness of care in oncology. In the Appendix, two examples of the recommendations produced though this project are presented: they refer to Trastuzumab in the treatment of early breast cancer and Fluoropirimide in the adjuvant therapy of colon cancer

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders’ trust for implementation of NAM evidence and AOPs into chemical risk assessment

Monitoring and evaluation of breast cancer screening programmes : Selecting candidate performance indicators

In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality

Testing the leadership and organizational change for implementation (LOCI) intervention in substance abuse treatment: A cluster randomized trial study protocol

© 2017 The Author(s). Background: Evidence-based practice (EBP) implementation represents a strategic change in organizations that requires effective leadership and alignment of leadership and organizational support across organizational levels. As such, there is a need for combining leadership development with organizational strategies to support organizational climate conducive to EBP implementation. The leadership and organizational change for implementation (LOCI) intervention includes leadership training for workgroup leaders, ongoing implementation leadership coaching, 360° assessment, and strategic planning with top and middle management regarding how they can support workgroup leaders in developing a positive EBP implementation climate. Methods: This test of the LOCI intervention will take place in conjunction with the implementation of motivational interviewing (MI) in 60 substance use disorder treatment programs in California, USA. Participants will include agency executives, 60 program leaders, and approximately 360 treatment staff. LOCI will be tested using a multiple cohort, cluster randomized trial that randomizes workgroups (i.e., programs) within agency to either LOCI or a webinar leadership training control condition in three consecutive cohorts. The LOCI intervention is 12months, and the webinar control intervention takes place in months 1, 5, and 8, for each cohort. Web-based surveys of staff and supervisors will be used to collect data on leadership, implementation climate, provider attitudes, and citizenship. Audio recordings of counseling sessions will be coded for MI fidelity. The unit of analysis will be the workgroup, randomized by site within agency and with care taken that co-located workgroups are assigned to the same condition to avoid contamination. Hierarchical linear modeling (HLM) will be used to analyze the data to account for the nested data structure. Discussion: LOCI has been developed to be a feasible and effective approach for organizations to create a positive climate and fertile context for EBP implementation. The approach seeks to cultivate and sustain both effective general and implementation leadership as well as organizational strategies and support that will remain after the study has ended. Development of a positive implementation climate for MI should result in more positive service provider attitudes and behaviors related to the use of MI and, ultimately, higher fidelity in the use of MI. Trial registration: This study is registered with Clinicaltrials.gov ( NCT03042832 ), 2 February 2017, retrospectively registered

Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable