Hot spot identification method based on Andrews curves: an application on the COVID-19 crisis effects on caregiver distress in neurocognitive disorder.

Identifying and locating areas - hot spots - that present high concentration of observations in a high-dimensional data set is crucial in many data processing and analysis methods and techniques, since observations that belong to the same hot spot share information and behave in a similar way. A useful tool towards that aim is the reduction of the data dimensionality and the graphical representation of them. In the present paper, a new method to identify and locate hot spots is proposed, based on the Andrews curves. Simulations results demonstrate the performance of the proposed method, which is also applied to a high-dimensional data set, regarding caregiver distress related to symptoms of people with neurocognitive disorder and to the mental effects of the recent outbreak of the COVID-19 pandemic.

Flexible designs for phase II comparative clinical trials involving two response variables.

The aim of phase II clinical trials is to determine whether an experimental treatment is sufficiently promising and safe to justify further testing. The need for reduced sample size arises naturally in phase II clinical trials owing to both technical and ethical reasons, motivating a significant part of research in the field during recent years, while another significant part of the research effort is aimed at more complex therapeutic schemes that demand the consideration of multiple endpoints to make decisions. In this paper, our attention is restricted to phase II clinical trials in which two treatments are compared with respect to two dependent dichotomous responses proposing some flexible designs. These designs permit the researcher to terminate the clinical trial when high rates of favorable or unfavorable outcomes are observed early enough requiring in this way a small number of patients. From the mathematical point of view, the proposed designs are defined on bivariate sequences of multi-state trials, and the corresponding stopping rules are based on various distributions related to the waiting time until a certain number of events appear in these sequences. The exact distributions of interest, under a unified framework, are studied using the Markov chain embedding technique, which appears to be very useful in clinical trials for the sample size determination. Tables of expected sample size and power are presented. The numerical illustration showed a very good performance for these new designs.

Smoking cessation effectiveness in smokers with COPD and asthma under real life conditions.

INTRODUCTION: Although smoking cessation is strongly indicated by international guidelines as an effective therapeutic tool for patients with COPD and Asthma, a large proportion of them do not quit smoking and they are regarded as a "difficult" target group. AIM: To study the effectiveness of an intensive smoking cessation program in smokers with COPD and asthma under real-life conditions. METHODS: 166 smokers with COPD, 120 smokers with asthma and 1854 control smokers attended the smoking cessation program in the out-patient patient Smoking Cessation Clinic of the Pulmonary Department in Athens University. Continuous Abstinence Rate (CAR) was evaluated in 3, 6, 9 and 12 months after the target quit date. RESULTS: Short-term CAR (in 3 months) was 49.4% for COPD smokers, 51.7% for asthmatic smokers and 48.0% for the control group of smokers. 12 months after the initial visit the CAR was 13.9%, 18.3% and 15.9%, respectively. No statistically significant differences between groups at any study period were found. Smokers with good compliance with the program had higher long-term CAR after 12 months: 37.7% in COPD smokers, 40.0% in asthmatic smokers and 39.3% in control smokers. High CAR was observed at all stages of COPD severity. CONCLUSION: The results support the view that smokers with respiratory obstructive airway diseases of any severity should be offered an intensive smoking cessation program with regular and long-term follow-up. This will help them to achieve high abstinence rates and prevent relapses.

Detection of biofilm production of Yersinia enterocolitica strains isolated from infected children and comparative antimicrobial susceptibility of biofilm versus planktonic forms.

BACKGROUND AND OBJECTIVES: The ability of Yersinia species to produce biofilms has not been hitherto systematically studied, although there is evidence, that Y. enterocolitica is able to form biofilms on inanimate surfaces. The present study aimed to detect the production of biofilms by 60 clinical strains of Y. enterocolitica and to compare the antimicrobial susceptibility of planktonic versus biofilm-forming bacteria. METHODS: Y. enterocolitica strains were collected from stool and blood cultures collected from ß-thalassaemic children, with gastroenteritis and/or septicemia. The isolated bacterial strains were grouped by biotyping and serotyping and the antimicrobial susceptibility of the planktonic forms was investigated by MIC determination. Biofilm formation was detected by the use of silicone disks and for the biofilm forming strains the minimum inhibitory concentration for bacterial regrowth (MICBR) of 11 clinically important antimicrobials was determined. The presence of the waaE, a gene reported to be related with biofilm formation was investigated in all the strains. RESULTS: All of 60 strains were positive for biofilm production by the use of silicone disks. The great majority of the biofilm forms were resistant to all the antimicrobials. In antimicrobial concentrations far higher than the CLSI breakpoints, bacterial regrowth from the biofilms was still possible. None of the strains bore the waaE gene. CONCLUSIONS: These results, indicate that biofilm formation by Y. enterocolitica might be an inherent feature. The presence of biofilms increased dramatically the MICBR in all antimicrobials. The way in which biofilms could contribute to Y. enterocolitica pathogenicity in humans is a matter needing further investigation.

Distribution of six effector protein virulence genes among Salmonella enterica enterica serovars isolated from children and their correlation with biofilm formation and antimicrobial resistance.

PURPOSE: Salmonella enterica enterica encodes a variety of virulence factors. Among them, the type III secretion system (TTSS) encoded in the Salmonella pathogenicity islands (SPIs) is required for induction of proinflammatory responses, invasion of intestinal epithelial cells, induction of cell death in macrophages, and elicitation of diarrhea. The presence of the effector protein genes sopB, sopD, sopE, sopE2, avrA, and sptP of the SPIs was analyzed in 194 S. enterica enterica strains belonging to 19 serovars. METHODS: S. enterica enterica strains were collected from children with gastroenteritis, either hospitalized or attending the outpatient clinic, aged 1-14 years. Nineteen different serotypes were included in the study. Serotyping, biofilm formation determination, and antimicrobial resistance of the planktonic as well as the biofilm forms of the strains have been reported previously. RESULTS: At least one virulence gene was present in all Salmonella isolates. Biofilm formation was statistically independent of any of the six genes. Strains lacking sopE and sopE2 were more resistant to all the antimicrobials. CONCLUSIONS: The association of the virulence genes with the antimicrobial resistance of Salmonella in general has been previously reported and is a matter of further investigation. For the clinical expression of pathogenicity in humans, the contribution of these genes is questionable, as some strains bearing only a single gene (either sptP or avrA) were still capable of causing gastroenteritis.

Comparative antimicrobial susceptibility of biofilm versus planktonic forms of Salmonella enterica strains isolated from children with gastroenteritis.

In the present study, 194 Salmonella enterica strains, isolated from infected children and belonging to various serotypes, were investigated for their ability to form biofilms and the biofilm forms of the isolated strains were compared to their corresponding planktonic forms with respect to the antimicrobial susceptibility. For the biofilm-forming strains, the minimum inhibitory concentration for bacterial regrowth (MICBR) from the biofilm of nine clinically applicable antimicrobial agents was determined, and the results were compared to the respective MIC values of the planktonic forms. One hundred and nine S. enterica strains out of 194 (56%) belonging to 13 serotypes were biofilm-forming. The biofilm forms showed increased antimicrobial resistance compared to the planktonic bacteria. The highest resistance rates of the biofilm bacteria were observed with respect to gentamicin (89.9%) and ampicillin (84.4%), and the lowest rates with respect to ciprofloxacin and moxifloxacin (2.8% for both). A remarkable shift of the MICBR(50) and MICBR(90) toward resistance was observed in the biofilm forms as compared to the respective planktonic forms. The development of new consensus methods for the determination of the antimicrobial susceptibility of biofilm forms seems to be a major research challenge. Further studies are required in order to elucidate the biofilm antimicrobial resistance mechanisms of the bacterial biofilms and their contribution to therapeutic failure in infections with in vitro susceptible bacteria.