Implementation of the EUCAST rapid antimicrobial susceptibility test (RAST) for carbapenemase/ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates, and its effect on mortality.

OBJECTIVES: With the rise in antimicrobial resistance, there is a growing demand for rapid antimicrobial susceptibility testing (RAST). In this study, we applied the EUCAST RAST method to ESBL/carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolates without using advanced identification systems and analysed the effect of this method on mortality rates Also the clinical impact of this method on patients infected with these bacteria and its effect on mortality rates were investigated. METHODS: RAST was used for clinical blood cultures containing carbapenemase/ESBL-producing E. coli and K. pneumoniae without advanced identification systems (e.g. MALDI TOF), with preliminary identification by simple diagnostic tests (predicted RAST, or p-RAST), and its categorical agreement was investigated. The impact of the method on mortality was analysed by comparing the clinical data of patients whose blood cultures were subject to p-RAST (p-RAST group, n = 49) and those who were not subject to p-RAST (non-RAST group, n = 145). RESULTS: p-RAST results were analysed based on 539 antibiotic-bacteria combinations. Total error rates at 4, 6 and 8 h of incubation were 2.9%, 3.9% and 3.8%, respectively. In the p-RAST group, patients who did not receive appropriate antibiotics (29/45, 59.1%) were switched to appropriate treatment within 8 h at the latest. In contrast, in the non-RAST group, treatment of patients who received inappropriate antibiotics (79/145, 54.5%) could be changed after at least 24 h. Mortality rates were lower in the p-RAST group than in the non-RAST group (28.6% versus 51.7%, P = 0.005). CONCLUSIONS: p-RAST can be used safely in hospital laboratories with high rates of antimicrobial resistance and can reduce mortality rates by shortening the transition time to appropriate treatment.

Translating knowledge on placebo and nocebo effects into clinical practice.

Introduction: Positive and negative treatment expectations are powerful modulators of health and treatment outcomes. A substantial part of treatment success is due to contextual factors modulating patient's expectations towards a treatment. Consequently, treatment expectations should be a target of therapeutic interventions themselves. Objectives: This article highlights the neurobiological underpinnings of treatment expectations as well as strategies to modulate contextual factors to optimize treatment outcomes in daily clinical settings. Methods: This clinical update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews the best available evidence and practice. Results: The effects of treatment expectations, also known as placebo and nocebo effects, are observed in various clinical conditions and physiological systems. However, most of our knowledge comes from the field of pain, where expectation effects substantially contribute to overall analgesic treatment outcomes. Experimental placebo analgesia paradigms provide the best illustration of how analgesic effects can be attributed not only to a pharmacological or specific treatment, but instead are the result of the expectation towards the treatment. The impact of expectations on treatment outcome is highly variable between individuals, and the identification of factors predicting an individual's response has proven to be challenging. Further research is required to provide personalized treatment strategies for the daily clinical practice. Conclusion: Patient's previous experiences and expectations are powerful modulators of treatment efficacy, tolerability, and adherence. By providing a comprehensive overview of recent advances in this field, this review offers valuable insights for clinicians and researchers seeking to improve patient-clinician interaction.

Coronavirus Disease 2019 in Patients with Asthma: Case Study from a Tertiary Center Regarding Their Phenotypes and Their Adherence to Asthma Treatment by Telemedicine.

OBJECTIVE: The aim of this study was to determine the prevalence and the characteristics of coronavirus disease 2019 (COVID-19) in a tertiary outpatient clinic of asthma patients, find the predisposing asthma phenotype to COVID-19, and to see their adherence to asthma treatment. MATERIAL AND METHODS: A retrospective, cross-sectional, real life study was conducted via phone interviews with the patients being followed in the asthma outpatient clinic. From the files of the patient information was obtained about their demographics, asthma phenotype, co-morbidity, prick tests, spirometry test results and their medications at the last visit before the COVID-19 pandemic. Information's about asthma exacerbations, ACT, asthma treatment adherence and history of COVID-19 were obtained via telephone interviews. RESULTS: Of the 573 patients with asthma, 13 (2.26%) had COVID-19 history. The mean age of patients with asthma and COVID-19 was 51.84±14.92 year. Two patients were on mepolizumab and one was on omalizumab treatment. Mean ACT was 19.84±2.73. Lack of adherence was reported in 8% of all patients with asthma compared to 23% in the patients who had COVID-19. Asthma exacerbation was seen during the course of SARS-CoV2 infection in 3 of 13 patients with asthma. Asthma exacerbations were reported during the period of one month following COVID-19 in 2 patients. CONCLUSION: The most common asthma phenotype in the cases of COVID-19 was obese phenotype. Rates of using biological agents and non-adherence to the treatment were found to be higher. Asthma exacerbation may be seen during course of COVID-19 albeit being less common.

Implementation of the EUCAST rapid antimicrobial susceptibility test (RAST) directly from positive blood culture bottles without the advanced identification systems.

OBJECTIVES: EUCAST published its recommendations for rapid antimicrobial susceptibility tests (RASTs) directly from positive signal blood culture (BC) bottles. The objective of the present study was to investigate the accuracy and applicability of the predicted RAST (p-RAST) method without using automated identification systems, and the effects of the results obtained with this method on the treatment decision of the clinician. METHODS: The RAST procedure was applied to positive BC samples between November 2020 and June 2021. The categorical results of the method were obtained by comparing the p-RAST results obtained at 4, 6 and 8 h of incubation according to predicted bacterial species with conventional methods and standard disc diffusion results. The effects of these results on the treatment decision of the clinician were evaluated retrospectively. The actual categorical results of the EUCAST RAST [standard RAST (s-RAST)] method were identified. RESULTS: The p-RAST and s-RAST results were analysed according to 145 and 111 isolates, respectively. The p-RAST total error rates were 3.0%, 3.1% and 2.8% at 4, 6 and 8 h of incubation, respectively, and the s-RAST total error rates were determined as 2.7%, 3.3% and 3.2%, respectively. With p-RAST's results, it was observed that effective escalation was performed in the antimicrobial treatment for 45 patients, and effective de-escalation could be performed in 32 patients, but it was recommended not to perform de-escalation. CONCLUSIONS: Even in a microbiology laboratory with limited facilities, reliable antimicrobial susceptibility test results can be obtained in a short time with the p-RAST method without using automated systems and antimicrobial choice can be guided in a shorter time.

Emergence of new manifestations during infliximab treatment in Behçet's syndrome.

OBJECTIVES: Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet's syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX. METHODS: A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX. RESULTS: Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients. CONCLUSION: New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations.

Oxytocin and Oxytocin Receptor Gene Regulation in Williams Syndrome: A Systematic Review.

Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes dysmorphic facial appearances, multiple congenital cardiovascular defects, delayed motor skills, and abnormalities in connective tissues and the endocrine system. The patients are mostly diagnosed with mild to moderate mental retardation, however, they have a hyper sociable, socially dis-inhibited, and outgoing personality, empathetic behavior, and are highly talkative. Oxytocin (OT), a neuropeptide synthesized at the hypothalamus, plays an important role in cognition and behavior, and is thought to be affecting WS patients' attitudes at its different amounts. Oxytocin receptor gene (OXTR), on chromosome 3p25.3, is considered regulating oxytocin receptors, via which OT exerts its effect. WS is a crucial disorder to understand gene, hormone, brain, and behavior associations in terms of sociality and neuropsychiatric conditions. Alterations to the WS gene region offer an opportunity to deepen our understandings of autism spectrum disorder, schizophrenia, anxiety, or depression. We aim to systematically present the data available of OT/OXTR regulation and expression, and the evidence for whether these mechanisms are dysregulated in WS. These results are important, as they predict strong epigenetic control over social behavior by methylation, single nucleotide polymorphisms, and other alterations. The comparison and collaboration of these studies may help to establish a better treatment or management approach for patients with WS if backed up with future research.

Diagnostic values of HNP 1-3 and procalcitonin levels in synovial fluid aspirates in the differential diagnosis between septic arthritis and noninfectious arthritis.

INTRODUCTION: Although early diagnosis of septic arthritis may reduce mortality rates, and limit unnecessary surgical interventions, clinical parameters alone are not adequate for making the diagnosis of septic arthritis. Therefore, relevant laboratory parameters are used to enhance diagnostic sensitivity. The aim of our study was to assist in making the diagnosis of septic arthritis, and prevent delays in the diagnosis. For this purpose; we aimed to determine the diagnostic values of human neutrophil peptides 1-3 (HNP 1-3) and procalcitonin (PCT) in synovial fluids of patients with arthritis. By comparing the HNP 1-3 and procalcitonin levels, as well as CRP, in synovial fluid aspirates, we evaluated the significance of these data in the differential diagnosis of septic arthritis from noninfectious arthritis. METHODS: A total of 67 adults consisting of 37 septic arthritis and 30 noninfectious arthritis patients were included in our study. As bioindicators; levels of HNP 1-3, PCT, synovial and serum CRP levels were found to have significant ROC areas in discriminating septic arthritis patients from noninfectious arthritis patients. RESULTS: As a result, synovial fluid HNP 1-3 levels were significantly higher in septic arthritis patients compared to noninfectious arthritis patients (p < 0.001). The sensitivity, specificity, and accuracy of HNP 1-3 levels in the diagnosis of septic and noninfectious arthritis were found as 86%, 87%, and 87%, respectively (AUC of the ROC curve = 0.828). CONCLUSIONS: It was decided that the level of HNP 1-3 in the synovial fluid can be used as an alternative indicator in the diagnosis of septic arthritis.

A study on solubilization of poorly soluble drugs by cyclodextrins and micelles: complexation and binding characteristics of sulfamethoxazole and trimethoprim.

The present study is focused on the characterization of solubilization of poorly soluble drugs, that is, sulfamethoxazole (SMX) and trimethoprim (TMP) by cyclodextrins (α-, ß-, and γ-CDs) and anionic surfactant sodium dodecyl sulfate (SDS). The phase solubility diagrams drawn from UV spectral measurements are of the A(L) type and indicate an enhancement of SMX and TMP solubility in the presence of CDs. Complex formation tendency of TMP with CDs followed the order: γ-CD > ß-CD > α-C. However, the complex formation constant values, for SMX-CD system yielded the different affinity and follow the order: ß-CD > γ-CD > α-CD. With taking into consideration of solubilization capacity of SDS micelles, it has been found that the solubility enhancement of TMP is much higher than that of SMX in the presence of SDS micelles. The binding constants of SMX and TMP obtained from the Benesi-Hildebrand equation are also confirmed by the estimated surface properties of SDS, employing the surface tension measurements. In order to elucidate the solubilization characteristics the surface tension measurements were also performed for nonionic surfactant Triton X-100. Polarity of the microenvironment and probable location of SMX and TMP were also discussed in the presence of various organic solvents.