Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is a major cause of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) shows promise for recurrent CDI, its mechanisms and long-term safety are not fully understood. Live biotherapeutic products (LBPs) using pre-defined bacterial consortia offer an alternative option, but the rational designing LBPs remains challenging. Here, we employ a computational pipeline and three metagenomic datasets to identify microbial strains for LBPs targeting CDI. We constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) and identified multiple potential protective nrMAGs, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these protective nrMAGs were found to play an important role in FMT success, and most top protective nrMAGs can be validated by various previous findings. Our results demonstrate a framework for selecting microbial strains targeting CDI, paving the way for the computational design of LBPs against other enteric infections.

Mental Health and (Online) Behaviors during the COVID-19 Pandemic in Spain: A Network-Based Approach.

The COVID-19 pandemic has contributed to the increase in mortality and morbidity rates globally, but it has also led to a generalized worsening of mental health and risk behaviors in different population groups regardless of the measures adopted by different governments. In this paper, using data from a Spanish survey of emotional well-being, we aim to explore through mixed graphical models the complex structure of relationships between the mental health of populations, their lifestyles, and forms of cultural and leisure consumption during the pandemic. The results bring to light some interesting findings, such as the association between teleworking and greater rest or greater stress with the use of social media, a variable that enables the connection with other mental health problems of greater severity. Increased physical activity and the consumption of streaming content at home, as well as increased care for family, friends, and neighbors, are some of the variables that show relevant associations. These findings highlight the usefulness and versatility of this network approach for the study of health behaviors and health outcomes, which offer the researcher a holistic and organic view of the relational structure of complex data characterized by high dimensionality and variables with different levels of measurement.

Best Practices in the Management of Clostridioides difficile Infection in Developing Nations.

Clostridioides difficile infection (CDI) is a well-known cause of hospital-acquired infectious diarrhea in developed countries, though it has not been a top priority in the healthcare policies of developing countries. In the last decade, several studies have reported a wide range of CDI rates between 1.3% and 96% in developing nations, raising the concern that this could represent a healthcare threat for these nations. This review defines developing countries as those with a human development index (HDI) below 0.8. We aim to report the available literature on CDI epidemiology, diagnostics, management, and prevention in developing countries. We identify limitations for CDI diagnosis and management, such as limited access to CDI tests and unavailable oral vancomycin formulation, and identify opportunities to enhance CDI care, such as increased molecular test capabilities and creative solutions for CDI. We also discuss infection prevention strategies, including antimicrobial stewardship programs and opportunities emerging from the COVID-19 pandemic, which could impact CDI care.

Understanding host immune responses in Clostridioides difficile infection: Implications for pathogenesis and immunotherapy.

Clostridioides difficile (C. difficile) is the predominant causative agent of nosocomial diarrhea worldwide. Infection with C. difficile occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of C. difficile's biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of C. difficile infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy-based treatments for CDI.

Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is one of the leading causes of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, its exact mechanisms of action and long-term safety are not fully understood. Defined consortia of clonal bacterial isolates, known as live biotherapeutic products (LBPs), have been proposed as an alternative therapeutic option. However, the rational design of LBPs remains challenging. Here, we employ a computational pipeline and three independent metagenomic datasets to systematically identify microbial strains that have the potential to inhibit CDI. We first constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) at the strain level. We then identified multiple potential protective nrMAGs that can be candidates for the design of microbial consortia targeting CDI, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these potential protective nrMAGs were found to play an important role in the success of FMT, and the majority of the top protective nrMAGs can be validated by various previously reported findings. Our results demonstrate a computational framework for the rational selection of microbial strains targeting CDI, paving the way for the computational design of microbial consortia against other enteric infections.

Identifying Barriers to the Acquisition of Knowledge about Skin Integrity Impairment in Nursing Students: An Educational Intervention.

BACKGROUND: Wound healing competence is implied in the nursing profession, but there is no standardized content regulation for wound care in university curricula. The primary objective of this study was to identify the barriers to the acquisition of knowledge about skin integrity impairment. METHODS: A quasi-experimental pre-test and post-test study with an ad hoc questionnaire involved 304 students (control: 165; intervention: 139) from June to July 2023. A 10-h educational intervention focused on skin integrity assessment and treatment was conducted. RESULTS: The control group, scoring 17 ± 0.22 out of a maximum of 61, achieved a significantly lower final test score (p < 0.001) compared to the wound care educational intervention group, with the pre-test group scoring 30 ± 0.76 and the post-test group scoring 43 ± 0.61. The educational intervention in wound care program improved nursing students' knowledge of prevention, assessment/diagnosis, treatment, lower limb wounds, and wound bed preparation by replacing the number of "Don't know" answers in the post-test group with correct answers. CONCLUSIONS: The barriers identified to the acquisition of knowledge about skin integrity impairment in nursing studies are the following: the transversality of teaching, the teaching and evaluation system, and the variability in the training of professionals and teachers in charge of their education. The educational intervention can be used to consolidate knowledge and to enhance students' self-confidence in caring for patients with wounds.

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Cytotoxicity and concentration of silver ions released from dressings in the treatment of infected wounds: a systematic review.

Introduction: Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential in vivo toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds. Methods: The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers. Results: 740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies. Conclusion: In vivo comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].

The Impact of Specialist Care on Teenage and Young Adult Patient-Reported Outcomes in England: A BRIGHTLIGHT Study.

Purpose: In England, health care policy promotes specialized age-appropriate cancer services for teenagers and young adults (TYA), for those aged 13-24 years at diagnosis. Specialist Principal Treatment Centers (PTCs) provide enhanced age-specific care for TYA, although many still receive all or some of their care in adult or children's cancer services. Our aim was to determine the patient-reported outcomes associated with TYA-PTC based care. Methods: We conducted a multicenter cohort study, recruiting 1114 TYA aged 13-24 years at diagnosis. Data collection involved a bespoke survey at 6,12,18, 24, and 36 months after diagnosis. Confounder adjusted analyses of perceived social support, illness perception, anxiety and depression, and health status, compared patients receiving NO-TYA-PTC care with those receiving ALL-TYA-PTC and SOME-TYA-PTC care. Results: Eight hundred and thirty completed the first survey. There was no difference in perceived social support, anxiety, or depression between the three categories of care. Significantly higher illness perception was observed in the ALL-TYA-PTC and SOME-TYA-PTC group compared to the NO-TYA-PTC group, (adjusted difference in mean (ADM) score on Brief Illness Perception scale 2.28 (95% confidence intervals [CI] 0.48-4.09) and 2.93 [1.27-4.59], respectively, p = 0.002). Similarly, health status was significantly better in the NO-TYA-PTC (ALL-TYA-PTC: ADM -0.011 [95%CI -0.046 to 0.024] and SOME-TYA-PTC: -0.054 [-0.086 to -0.023]; p = 0.006). Conclusion: The reason for the difference in perceived health status is unclear. TYA who accessed a TYA-PTC (all or some care) had higher perceived illness. This may reflect greater education and promotion of self-care by health care professionals in TYA units.

Epidemiology, mortality, and health service use of local-level multimorbidity patterns in South Spain.

Multimorbidity -understood as the occurrence of chronic diseases together- represents a major challenge for healthcare systems due to its impact on disability, quality of life, increased use of services and mortality. However, despite the global need to address this health problem, evidence is still needed to advance our understanding of its clinical and social implications. Our study aims to characterise multimorbidity patterns in a dataset of 1,375,068 patients residing in southern Spain. Combining LCA techniques and geographic information, together with service use, mortality, and socioeconomic data, 25 chronicity profiles were identified and subsequently characterised by sex and age. The present study has led us to several findings that take a step forward in this field of knowledge. Specifically, we contribute to the identification of an extensive range of at-risk groups. Moreover, our study reveals that the complexity of multimorbidity patterns escalates at a faster rate and is associated with a poorer prognosis in local areas characterised by lower socioeconomic status. These results emphasize the persistence of social inequalities in multimorbidity, highlighting the need for targeted interventions to mitigate the impact on patients' quality of life, healthcare utilisation, and mortality rates.

Discovery and characterisation of socially polarised communities on social media.

Social polarisation processes have become a central phenomenon for the explanation of population behavioural dynamics in today's societies. Although recent works offer solutions for the detection of polarised political communities in social media, there is still a lack of works that allow an adequate characterization of the specific topics on which these divides between social groups are articulated. Our study aims to discover and characterise antagonistic communities on Twitter based on a method that combines the identification of authorities and textual classifiers around three public debates that have recently produced major controversies: (1) vaccination; (2) climate change; and (3) abortion. The proposed method allows the capture of polarised communities with little effort, requiring only the selection of some terms that characterise the topic and some initial authorities. Our findings show that the processes of social polarisation can vary considerably depending on the subject on which the debates are articulated. Specifically, polarisation manifests more prominently in the realms of vaccination and abortion, whereas this divide is less apparent in the context of climate change.

Corrigendum: Illness perceptions of COVID-19 in Europe: predictors, impacts and temporal evolution.

[This corrects the article DOI: 10.3389/fpsyg.2021.640955.].

Social determinants of multimorbidity patterns: A systematic review.

Social determinants of multimorbidity are poorly understood in clinical practice. This review aims to characterize the different multimorbidity patterns described in the literature while identifying the social and behavioral determinants that may affect their emergence and subsequent evolution. We searched PubMed, Embase, Scopus, Web of Science, Ovid MEDLINE, CINAHL Complete, PsycINFO and Google Scholar. In total, 97 studies were chosen from the 48,044 identified. Cardiometabolic, musculoskeletal, mental, and respiratory patterns were the most prevalent. Cardiometabolic multimorbidity profiles were common among men with low socioeconomic status, while musculoskeletal, mental and complex patterns were found to be more prevalent among women. Alcohol consumption and smoking increased the risk of multimorbidity, especially in men. While the association of multimorbidity with lower socioeconomic status is evident, patterns of mild multimorbidity, mental and respiratory related to middle and high socioeconomic status are also observed. The findings of the present review point to the need for further studies addressing the impact of multimorbidity and its social determinants in population groups where this problem remains invisible (e.g., women, children, adolescents and young adults, ethnic groups, disabled population, older people living alone and/or with few social relations), as well as further work with more heterogeneous samples (i.e., not only focusing on older people) and using more robust methodologies for better classification and subsequent understanding of multimorbidity patterns. Besides, more studies focusing on the social determinants of multimorbidity and its inequalities are urgently needed in low- and middle-income countries, where this problem is currently understudied.

The impact of government actions and risk perception on the promotion of self-protective behaviors during the COVID-19 pandemic.

INTRODUCTION: We aim to understand the factors that drive citizens of different countries to adhere to recommended self-protective behaviors during the COVID-19 pandemic. METHODS: Survey data was obtained through the COVID-19 Impact project. We selected countries that presented a sufficiently complete time series and a statistically relevant sample for running the analysis: Cyprus, Germany, Greece, Ireland, Latvia, Spain, Switzerland, the United Kingdom, and the United States of America. To identify country-specific differences in self-protective behaviors, we used previous evidence and change-point detection analysis to establish variations across participating countries whose effect was then assessed by means of interrupted series analysis. RESULTS: A high level of compliance with health and governmental authorities' recommendations were generally observed in all included countries. The level of stress decreased near the period when countries such as Cyprus, Greece or the United Kingdom relaxed their prevention behavior recommendations. However, this relaxation of behaviors did not occur in countries such as Germany, Ireland, or the United States. As observed in the change-point detection analysis, when the daily number of recorded COVID-19 cases decreased, people relaxed their protective behaviors (Cyprus, Greece, Ireland), although the opposite trend was observed in Switzerland. DISCUSSION: COVID-19 self-protective behaviors were heterogeneous across countries examined. Our findings show that there is probably no single winning strategy for exiting future health crises, as similar interventions, aimed to promote self-protective behaviors, may be received differently depending on the specific population groups and on the particular geographical context in which they are implemented.

Predictors of changing patterns of adherence to containment measures during the early stage of COVID-19 pandemic: an international longitudinal study.

BACKGROUND: Identifying common factors that affect public adherence to COVID-19 containment measures can directly inform the development of official public health communication strategies. The present international longitudinal study aimed to examine whether prosociality, together with other theoretically derived motivating factors (self-efficacy, perceived susceptibility and severity of COVID-19, perceived social support) predict the change in adherence to COVID-19 containment strategies. METHOD: In wave 1 of data collection, adults from eight geographical regions completed online surveys beginning in April 2020, and wave 2 began in June and ended in September 2020. Hypothesized predictors included prosociality, self-efficacy in following COVID-19 containment measures, perceived susceptibility to COVID-19, perceived severity of COVID-19 and perceived social support. Baseline covariates included age, sex, history of COVID-19 infection and geographical regions. Participants who reported adhering to specific containment measures, including physical distancing, avoidance of non-essential travel and hand hygiene, were classified as adherence. The dependent variable was the category of adherence, which was constructed based on changes in adherence across the survey period and included four categories: non-adherence, less adherence, greater adherence and sustained adherence (which was designated as the reference category). RESULTS: In total, 2189 adult participants (82% female, 57.2% aged 31-59 years) from East Asia (217 [9.7%]), West Asia (246 [11.2%]), North and South America (131 [6.0%]), Northern Europe (600 [27.4%]), Western Europe (322 [14.7%]), Southern Europe (433 [19.8%]), Eastern Europe (148 [6.8%]) and other regions (96 [4.4%]) were analyzed. Adjusted multinomial logistic regression analyses showed that prosociality, self-efficacy, perceived susceptibility and severity of COVID-19 were significant factors affecting adherence. Participants with greater self-efficacy at wave 1 were less likely to become non-adherence at wave 2 by 26% (adjusted odds ratio [aOR], 0.74; 95% CI, 0.71 to 0.77; P < .001), while those with greater prosociality at wave 1 were less likely to become less adherence at wave 2 by 23% (aOR, 0.77; 95% CI, 0.75 to 0.79; P = .04). CONCLUSIONS: This study provides evidence that in addition to emphasizing the potential severity of COVID-19 and the potential susceptibility to contact with the virus, fostering self-efficacy in following containment strategies and prosociality appears to be a viable public health education or communication strategy to combat COVID-19.

Preservation of the Innate Immune Response to Clostridioides difficile Infection in Hospitalized Immunocompromised Patients.

Background: Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods: We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-10, IL-15, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. Results: One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1ß and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1ß demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). Conclusions: In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients.

Profiling Hesitancy to COVID-19 Vaccinations in Six European Countries: Behavioral, Attitudinal and Demographic Determinants.

Vaccination hesitancy is an important barrier for the effective control of the COVID-19 pandemic. Identifying determinants of COVID-19 vaccination hesitancy is essential in order to reduce mortality rates. Further, given the variability of the factors and the different recommendations used in each country, it is important to conduct cross-country research to profile individuals who are hesitant toward COVID-19 vaccinations. This cross-sectional study aimed to examine cross-country differences and the behavioral, attitudinal and demographic characteristics of vaccine hesitant individuals. Adults living in six European countries (Cyprus, France, Germany, Italy, Poland, and Spain) were eligible to participate. A total of 832 individuals completed the online survey, with 17.9% reporting being hesitant to COVID-19 vaccination. Vaccine accepters were significantly older (M = 38.9, SD = 14.3), more educated (master/postgraduate studies) and lived in a place with a higher number of residents (>500,000 people) compared to those hesitant to COVID-19 vaccination. Discriminant analysis confirmed that the hesitant profile includes a person of younger age, living alone in smaller communities, and without children. Additionally, hesitant participants reported COVID-19-specific characteristics such as lower institutional trust, less adherence to COVID-19 protective behaviors and higher pandemic fatigue. When tackling COVID-19 vaccination hesitancy both socio-demographic and behavioral/attitudinal aspects should be taken into account. Stakeholders are advised to implement targeted vaccination programs while at the same time building trust with population illness cognitions addressed in order to reduce hesitancy rates. Further, stakeholders and public health authorities in each country are suggested to target interventions according to different population characteristics as behavioral and attitudinal determinants of COVID-19 vaccination hesitancy differed between countries.

Stool Interleukin-1ß Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea.

BACKGROUND: Despite advances in the understanding and diagnosis of Clostridioides difficile infection (CDI), clinical distinction within the colonization-infection continuum remains an unmet need. METHODS: By measuring stool cytokines and antitoxin antibodies in well-characterized cohorts of CDI (diarrhea, nucleic acid amplification test [NAAT] positive), non-CDI diarrhea (NCD; diarrhea, NAAT negative), asymptomatic carriers (ASC; no diarrhea, NAAT positive) and hospital controls (CON; no diarrhea, NAAT negative), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and antitoxin antibody with stool toxin concentrations and disease severity. RESULTS: Stool interleukin (IL) 1ß, stool immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-toxin A had higher (P < .0001) concentrations in CDI (n = 120) vs ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas under the receiver operating characteristic curve (ROC-AUCs) for IL-1ß, IgA, and IgG anti-toxin A were 0.88, 0.83, and 0.83, respectively. A multipredictor model including IL-1ß and IgA anti-toxin A achieved an ROC-AUC of 0.93. Stool IL-1ß concentrations were higher in CDI compared to NCD (n = 75) (P < .0001) and NCD + ASC+ CON (CON, n = 75) (P < .0001), with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1ß had positive correlations with toxins A (ρA = +0.55) and B (ρB = +0.49) in CDI (P < .0001) but not in ASC (P > .05). CONCLUSIONS: Stool concentrations of the inflammasome pathway, proinflammatory cytokine IL-1ß, can accurately differentiate CDI from asymptomatic carriage and NCD, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1ß in CDI but not in asymptomatic carriers.