Mechanism mapping to advance research on implementation strategies.

Elvin Hsing Geng and colleagues discuss mechanism mapping and its utility in conceptualizing and understanding how implementation strategies produce desired effects.

Safely Reducing Hospitalizations for Anaphylaxis in Children Through an Evidence-Based Guideline.

BACKGROUND: Emergency department visits for anaphylaxis have increased considerably over the past few decades, especially among children. Despite this, anaphylaxis management remains highly variable and contributes to significant health care spending. On the basis of emerging evidence, in this quality improvement project we aimed to safely decrease hospitalization rates, increase the use of cetirizine, and decrease use of corticosteroids for children with anaphylaxis by December 31, 2019. METHODS: A multipronged intervention strategy including a revised evidence-based guideline was implemented at a tertiary children's teaching hospital by using the Model for Improvement. Statistical process control was used to evaluate for changes in key measures. Length of stay and unplanned return visits within 72 hours were monitored as process and balancing measures, respectively. As a national comparison, hospitalization rates were compared with other hospitals' data from the Pediatric Health Information System. RESULTS: Hospitalizations decreased significantly from 28.5% to 11.2% from preimplementation to implementation, and the balancing measure of 72-hour revisits was stable. The proportion of patients receiving cetirizine increased significantly from 4.2% to 59.7% and use of corticosteroids decreased significantly from 72.6% to 32.4% in patients without asthma. The proportion of patients meeting length of stay criteria increased from 53.3% to 59.9%. Hospitalization rates decreased nationally over time. CONCLUSIONS: We reduced hospitalizations for anaphylaxis by 17.3% without concomitant increases in revisits, demonstrating that unnecessary hospitalizations can be safely avoided. The use of a local evidence-based guideline paired with close outcome monitoring and sustained messaging and feedback to clinicians can effectively improve anaphylaxis management.

Use of Real-World Data and Evidence in Drug Development of Medicinal Products Centrally Authorized in Europe in 2018-2019.

Real-world data/real-world evidence (RWD/RWE) are considered to have a great potential to complement, in some cases, replace the evidence generated through randomized controlled trials. By tradition, use of RWD/RWE in the postauthorization phase is well-known, whereas published evidence of use in the pre-authorization phase of medicines development is lacking. The primary aim of this study was to identify and quantify the role of potential use of RWD/RWE (RWE signatures) during the pre-authorization phase, as presented in the initial marketing authorization applications of new medicines centrally evaluated with a positive opinion in 2018-2019 (n = 111) by the European Medicines Agency (EMA). Data for the study was retrieved from the evaluation overviews of the European Public Assessment Reports (EPARs), which reflect the scientific conclusions of the assessment process and are accessible through the EMA website. RWE signatures were extracted into an RWE Data Matrix, including 11 categories divided over 5 stages of the drug development lifecycle. Nearly all EPARs included RWE signatures for the discovery (98.2%) and life-cycle management (100.0%). Half of them included RWE signatures for the full development phase (48.6%) and for supporting regulatory decisions at the registration (46.8%), whereas over a third (35.1%) included RWE signatures for the early development. RWE signatures were more often seen for orphan and conditionally approved medicines. Oncology, hematology, and anti-infectives stood out as therapeutic areas with most RWE signatures in their full development phase. The findings bring unprecedented insights about the vast use of RWD/RWE in drug development supporting the regulatory decision making.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Moving towards a Treatable Traits model of care for the management of obstructive airways diseases.

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airways diseases. Both are complex and heterogeneous. Traditionally, clinical guidelines have advocated a stepwise approach to pharmacotherapy of asthma and COPD, but there is increasing realization that both require a more personalized and precise management approach. To this end, a management strategy based on the so-called Treatable Traits has been proposed. Emerging evidence suggests that this model improves relevant outcomes in patients with chronic airway diseases but further research is needed to guide implementation. This review discusses the challenges, opportunities, and hurdles that its implementation will have to face.

Clinical Epidemiology in China series. Paper 2: Promoting GRADE at the national level: The experience from China.

OBJECTIVE: To share the experience of promoting GRADE in China. STUDY DESIGN AND SETTING: We designed the study and collected data on the following three aspects of the GRADE in China: the key activities related to GRADE, the main achievements of the GRADE, and potential challenges and future opportunities. RESULTS: Three GRADE centres have been established in China since 2011. Seventeen articles of the GRADE working group have been translated and published in Chinese, and 31 articles have been written by Chinese scientists in Chinese to introduce and interpret the GRADE approach so far. More than 50 GRADE workshops and meetings have been held by GRADE centres in China, covering two-thirds of all provinces and autonomous regions of China. The percentages of societies from the Chinese Medical Association (CMA) and the Chinese Medical Doctor Association (CMDA) that used the GRADE system to develop guidelines were 30% and 18%, respectively. CONCLUSION: Over the past decade, China has made progress in promoting the GRADE system and Chinese GRADE centres have made a significant contribution.

Covid-19 pandemic: Perspectives on management.

The pandemic COVID-19 presents a major challenge to identify effective drugs for treatment. Clinicians need evidence based on randomized trials regarding effective medical treatments for this infection. Currently no effective therapies exist for the progression of the mild forms to severe disease. Knowledge however is rapidly expanding. Remdesivir, an anti- retroviral agent has in vitro activity against this virus and has shown to decrease the duration of ICU care in patients with severe disease, while low dose dexamethasone also showed a decrease in the duration of stay in cases of severe disease requiring assisted ventilation. At the time of writing this article, two mRNA-based vaccines have shown an approximate 95 % efficacy in preventing infection in large clinical trials. At least one of these drugs has regulatory permission for vaccination in high-income countries. Low and middle-income countries may have difficulties in initiating vaccine programs on large scales because of availability, costs, refrigeration and dissemination. Adequately powered randomized trials are required for drugs with in vitro activity against the virus. Supportive care should be provided for stable, hypoxia and pneumonia free patients on imaging. Vaccines are of obvious benefit and given the preliminary evidence of the efficacy of over 95 %, Low and middle-income countries must develop links with the WHO COVAX program to ensure global distribution of vaccines.

Predicting innovative firms using web mining and deep learning.

Evidence-based STI (science, technology, and innovation) policy making requires accurate indicators of innovation in order to promote economic growth. However, traditional indicators from patents and questionnaire-based surveys often lack coverage, granularity as well as timeliness and may involve high data collection costs, especially when conducted at a large scale. Consequently, they struggle to provide policy makers and scientists with the full picture of the current state of the innovation system. In this paper, we propose a first approach on generating web-based innovation indicators which may have the potential to overcome some of the shortcomings of traditional indicators. Specifically, we develop a method to identify product innovator firms at a large scale and very low costs. We use traditional firm-level indicators from a questionnaire-based innovation survey (German Community Innovation Survey) to train an artificial neural network classification model on labelled (product innovator/no product innovator) web texts of surveyed firms. Subsequently, we apply this classification model to the web texts of hundreds of thousands of firms in Germany to predict whether they are product innovators or not. We then compare these predictions to firm-level patent statistics, survey extrapolation benchmark data, and regional innovation indicators. The results show that our approach produces reliable predictions and has the potential to be a valuable and highly cost-efficient addition to the existing set of innovation indicators, especially due to its coverage and regional granularity.

Validity and reliability of the Noor Evidence-Based Medicine Questionnaire: A cross-sectional study.

BACKGROUND: Evidence-based medicine (EBM) is a widely accepted scientific advancement in clinical settings that helps achieve better, safer, and more cost-effective healthcare. However, presently, validated instruments to evaluate healthcare professionals' attitude and practices toward implementing EBM are not widely available. Therefore, the present study aimed to determine the validity and reliability of a newly developed knowledge, attitude, and practice (KAP) questionnaire on EBM for use among healthcare professionals. METHODS: The Noor Evidence-Based Medicine Questionnaire was tested among physicians in a government hospital between July and August 2018. Exploratory factor analysis and internal consistency reliability-based Cronbach's alpha statistic were conducted. RESULTS: The questionnaire was distributed among 94 physicians, and 90 responded (response rate of 95.7%). The initial number of items in the KAP domains of the Noor Evidence-Based Medicine Questionnaire were 15, 17, and 13, respectively; however, two items in the practice domain with communalities <0.25 and factor loadings <0.4 were removed. The factor structure accounted for 52.33%, 66.29%, and 55.39% of data variance in the KAP domains, respectively. Cronbach's alpha values were 0.81, 0.81, and 0.84 for KAP domains, respectively, indicating high reliability. CONCLUSIONS: This questionnaire can be used to evaluate the knowledge, attitudes, and behaviour of healthcare professionals toward EBM. Future testing of this questionnaire among other medical personnel groups will help expand the scope of this tool.

Back and neck pain: in support of routine delivery of non-pharmacologic treatments as a way to improve individual and population health.

Chronic back and neck pain are highly prevalent conditions that are among the largest drivers of physical disability and cost in the world. Recent clinical practice guidelines recommend use of non-pharmacologic treatments to decrease pain and improve physical function for individuals with back and neck pain. However, delivery of these treatments remains a challenge because common care delivery models for back and neck pain incentivize treatments that are not in the best interests of patients, the overall health system, or society. This narrative review focuses on the need to increase use of non-pharmacologic treatment as part of routine care for back and neck pain. First, we present the evidence base and summarize recommendations from clinical practice guidelines regarding non-pharmacologic treatments. Second, we characterize current use patterns for non-pharmacologic treatments and identify potential barriers to their delivery. Addressing these barriers will require coordinated efforts from multiple stakeholders to prioritize evidence-based non-pharmacologic treatment approaches over low value care for back and neck pain. These stakeholders include patients, health care providers, health care organizations, administrators, payers, policymakers and researchers.

Utilizing Artificial Intelligence to Manage COVID-19 Scientific Evidence Torrent with Risklick AI: A Critical Tool for Pharmacology and Therapy Development.

INTRODUCTION: The SARS-CoV-2 pandemic has led to one of the most critical and boundless waves of publications in the history of modern science. The necessity to find and pursue relevant information and quantify its quality is broadly acknowledged. Modern information retrieval techniques combined with artificial intelligence (AI) appear as one of the key strategies for COVID-19 living evidence management. Nevertheless, most AI projects that retrieve COVID-19 literature still require manual tasks. METHODS: In this context, we pre-sent a novel, automated search platform, called Risklick AI, which aims to automatically gather COVID-19 scientific evidence and enables scientists, policy makers, and healthcare professionals to find the most relevant information tailored to their question of interest in real time. RESULTS: Here, we compare the capacity of Risklick AI to find COVID-19-related clinical trials and scientific publications in comparison with clinicaltrials.gov and PubMed in the field of pharmacology and clinical intervention. DISCUSSION: The results demonstrate that Risklick AI is able to find COVID-19 references more effectively, both in terms of precision and recall, compared to the baseline platforms. Hence, Risklick AI could become a useful alternative assistant to scientists fighting the COVID-19 pandemic.

Precision oncology in metastatic colorectal cancer - from biology to medicine.

Remarkable progress has been made in the development of biomarker-driven targeted therapies for patients with multiple cancer types, including melanoma, breast and lung tumours, although precision oncology for patients with colorectal cancer (CRC) continues to lag behind. Nonetheless, the availability of patient-derived CRC models coupled with in vitro and in vivo pharmacological and functional analyses over the past decade has finally led to advances in the field. Gene-specific alterations are not the only determinants that can successfully direct the use of targeted therapy. Indeed, successful inhibition of BRAF or KRAS in metastatic CRCs driven by activating mutations in these genes requires combinations of drugs that inhibit the mutant protein while at the same time restraining adaptive resistance via CRC-specific EGFR-mediated feedback loops. The emerging paradigm is, therefore, that the intrinsic biology of CRC cells must be considered alongside the molecular profiles of individual tumours in order to successfully personalize treatment. In this Review, we outline how preclinical studies based on patient-derived models have informed the design of practice-changing clinical trials. The integration of these experiences into a common framework will reshape the future design of biology-informed clinical trials in this field.

[2020: Evidence-Based Medicine odyssey. The fall and rise of evidence-based medicine in the year of coronavirus.] / Odissea per la evidence-based medicine. Caduta e rinascita nell'anno del coronavirus.

It was a very dark year for EBM. One of the side effects of the Covid-19 pandemic is a severe compression of the evidences. Here are some worrying events. May 2020: the saga of hydroxychloroquine. October 2020: the nitazoxanide case. November 2020: Trump Administration Interferes on Expert Opinion. December 2020: the results of the trials on the first two vaccines were announced in press releases, leaving many scientific uncertainties. Peter Piot, head of the London School of Hygiene & Tropical Medicine noted that none of the CoViD-19 vaccines have offered much data to date. «It is frustrating that all of these announcements are delivered via press release, and not give us a chance to review the actual data. We desperately need total transparency on evidence and data¼, says Piot. Better now to relaunch the spread of EBM. In the issue, we have included the best EBM-based readings from the Club for Evidence-Based in Gastroenterology & Hepatology (ebgh.it).

Antithrombotic therapy in patients with COVID-19? -Rationale and Evidence.

In patients with severe or critical Coronavirus disease 2019 (COVID-19) manifestations, a thromboinflammatory syndrome, with diffuse microvascular thrombosis, is increasingly evident as the final step of pro-inflammatory cytokines storm. Actually, no proven effective therapies for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exist. Preliminary observations on anticoagulant therapy appear to be associated with better outcomes in moderate and severe COVID-19 patients with signs of coagulopathy and in those requiring mechanical ventilation. The pathophysiology underlying the prothrombotic state elicited by SARS-CoV-2 outlines possible protective mechanisms of antithrombotic therapy (in primis anticoagulants) for this viral illness. The indications for antiplatelet/anticoagulant use (prevention, prophylaxis, therapy) are guided by the clinical context and the COVID-19 severity. We provide a practical approach on antithrombotic therapy management for COVID-19 patients from a multidisciplinary point of view.

A New Approach to Evidence Synthesis in Traumatic Brain Injury: A Living Systematic Review.

Living systematic reviews (LSRs) are online summaries of health care research that are updated as new research becomes available. This new development in evidence synthesis is being trialled as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project. We will develop and sustain an international TBI knowledge community that maintains up-to-date, high quality LSRs of the current state of knowledge in the most important questions in TBI. Automatic search updates will be run three-monthly, and newly identified studies incorporated into the review. Review teams will seek to publish journal updates at regular intervals, with abridged updates available more frequently online. Future project stages include the integration of LSR and other study findings into "living" clinical practice guidance. It is hoped these efforts will go some way to bridging current temporal disconnects between evidence, guidelines, and practice in TBI.