The philosophy of Evidence-based Medicine

Evidence-based Medicine is the application of the best evidence available in the care of individual patients, using mathematical estimates of probability and risk. Although elements of EBM have appeared centuries ago, the term Evidence-based Medicine has been used for 10 years only. The spread of EBM followed studies which had shown that in contemporary medicine a significant proportion of interventions, although they are considered as the standard of care, have not proven efficacy. The two principles of EBM are that evidence alone is not enough for clinical decision making and that there is a hierarchy of evidence. Evidence-based medicine can be practiced in up to five steps i.e. formulating answerable clinical questions, searching for the best available evidence, critically appraising the evidence, applying the evidence in clinical situations and evaluating one’s effectiveness and efficiency. One does not have to go through all steps in practicing EBM, e.g. there now exist the so called secondary publications which are systematic reviews or meta-analyses of all available studies on a clinical problem or journals entirely devoted in appraisal of original studies. Notwithstanding the “success” of EBM there is a strong current of criticism on subjects practical and philosophical alike. The strongest point against EBM however is that there is no evidence that practicing EBM improves patients’ outcomes. In our opinion, EBM is a very useful instrument with wide-ranging applications in the practice of medicine. However EBM is neither a new scientific field nor a paradigm shift in contemporary medicine. As an empirical approach to clinical problems, EBM does not produce scientific knowledge and therefore it should not be given more room than it deserves, neglecting basic or clinical research. “...between man and angel there is this difference, that an angel perceives the truth by simple apprehension, whereas man becomes acquainted with a simple truth by a process from manifold data” Thomas Aquinas, Summa Theologica

Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study

© 2022 Elsevier Ltd. All rights reserved.[Background] The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.[Methods] In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.[Findings] 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04–1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05–1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4–30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.[Interpretation] Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.Scynexis.Peer reviewe

Antibiotic Stewardship in Surgical Departments

Antimicrobial resistance (AMR) has emerged as one of the leading public health threats of the 21st century. New evidence underscores its significance in patients’ morbidity and mortality, length of stay, as well as healthcare costs. Globally, the factors that contribute to antimicrobial resistance include social and economic determinants, healthcare governance, and environmental interactions with impact on humans, plants, and animals. Antimicrobial stewardship (AS) programs have historically overlooked surgical teams as they considered them more difficult to engage. This review aims to summarize the evolution and significance of AS in surgical wards, including the surgical intensive care unit (SICU) and the role of diagnostic stewardship (DS). The contribution of AS team members is presented. The new diagnostic modalities and the new technologies including artificial intelligence (AI) are also reviewed

Reactivation of Varicella Zoster Virus after Vaccination for SARS-CoV-2

Seven immunocompetent patients aged &gt; 50 years old presented with herpes zoster (HZ) infection in a median of 9 days (range 7-20) after vaccination against SARS-CoV-2. The occurrence of HZ within the time window 1-21 days after vaccination defined for increased risk and the reported T cell-mediated immunity involvement suggest that COVID-19 vaccination is a probable cause of HZ. These cases support the importance of continuing assessment of vaccine safety during the ongoing massive vaccination for the COVID-19 pandemic and encourage reporting and communication of any vaccination-associated adverse event

Encephalopathy in an adult with cat-scratch disease.

We report the case of a 53-year-old healthy man, presenting with confusion. The patient had been clinically diagnosed with cat-scratch disease (CSD) and prescribed a 10-day course of doxycycline orally. Approximately a week after he had completed the treatment, he was admitted to our department with confusion. Neurological examination revealed expressive dysphasia with no motor or sensory deficits. Cerebrospinal fluid (CSF) examination showed only increased content. Imaging with CT and MRI of the brain did not reveal any abnormalities, and funduscopy was normal. Serology confirmed Bartonella henselae infection. CSD-associated encephalopathy was confirmed based on the clinical manifestations, CSF findings and positive serology. The patient was treated with a combination of doxycycline and rifampin and he rapidly improved with complete neurological recovery within 7 days. Encephalopathy is an unusual manifestation of CSD in adults with excellent prognosis

Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond

In the era of precision medicine, antibody-based therapeutics are rapidly enriched with emerging advances and new proof-of-concept formats. In this context, antibody-drug conjugates (ADCs) have evolved to merge the high selectivity and specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of attached payloads. So far, ten ADCs have been approved by FDA for oncological indications and many others are currently being tested in clinical and preclinical level. This paper summarizes the essential components of ADCs, from their functional principles and structure up to their limitations and resistance mechanisms, focusing on all latest bioengineering breakthroughs such as bispecific mAbs, dual-drug platforms as well as novel linkers and conjugation chemistries. In continuation of our recent review on anticancer implication of ADC’s technology, further insights regarding their potential usage outside of the oncological spectrum are also presented. Better understanding of immunoconjugates could maximize their efficacy and optimize their safety, extending their use in everyday clinical practice

Molecular screening of cat and dog ectoparasites for the presence of Bartonella spp. in Attica, Greece.

The purpose of this study was the molecular detection of Bartonella spp. in fleas and ticks parasitizing cats and dogs from 39 locations in Attica, Greece. One hundred and forty five ectoparasites (104 fleas and 41 ticks) from 92 cats and 53 dogs were investigated individually using PCRs targeting the 16S-23S ribosomal RNA intergenic spacer (ITS) and the citrate synthase (gltA) genetic loci. Bartonella spp. were detected in 14 out of 104 fleas (13.5%) and in none of the ticks examined. Consequent sequence analysis of the amplicons from the two loci identified 3 strains as Bartonella henselae, and 11 as Bartonella clarridgeiae. Οur study demonstrates the presence of B. henselae and B. clarridgeiae in Ctenocephalides felis fleas from cat and dog in Greece. We also report a novel ITS sequence for B. clarridgeiae. Considering that fleas could pose a risk for human bartonellosis from their infected hosts, further studies on the public health risk of Bartonella presence in animal ectoparasites are warranted