Clostridioides difficile canonical L,D-transpeptidases catalyze a novel type of peptidoglycan cross-links and are not required for beta-lactam resistance.

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, an essential component of the bacteria cell envelope. Previous work has revealed that C. difficile peptidoglycan has an unusual composition. It mostly contains 3-3 cross-links, catalyzed by enzymes called L,D-transpeptidases (Ldts) that are poorly inhibited by beta-lactams. It was therefore hypothesized that peptidoglycan polymerization by these enzymes could underpin antibiotic resistance. Here, we investigated the catalytic activity of the three canonical Ldts encoded by C. difficile (LdtCd1, LdtCd2, and LdtCd3) in vitro and explored their contribution to growth and antibiotic resistance. We show that two of these enzymes catalyze the formation of novel types of peptidoglycan cross-links using meso-diaminopimelic acid both as a donor and an acceptor, also observed in peptidoglycan sacculi. We demonstrate that the simultaneous deletion of these three genes only has a minor impact on both peptidoglycan structure and resistance to beta-lactams. This unexpected result therefore implies that the formation of 3-3 peptidoglycan cross-links in C. difficile is catalyzed by as yet unidentified noncanonical Ldt enzymes.

Clostridioides difficile positivity rate and PCR ribotype distribution on retail potatoes in 12 European countries, January to June 2018.

BackgroundWhile human-to-human transmission of Clostridioides difficile occurs often, other infection sources, including food, animals and environment, are under investigation.AimWe present a large study on C. difficile in a food item in Europe, encompassing 12 European countries (Austria, France, Greece, Ireland, Italy, the Netherlands, Poland, Slovakia, Spain, Sweden, Romania and the United Kingdom).MethodsPotato was selected because of availability, ease of sampling and high C. difficile positivity rates. Identical protocols for sampling and isolation were used, enabling a direct comparison of the C. difficile positivity rate.ResultsFrom C. difficile-positive potato samples (33/147; 22.4%), we obtained 504 isolates, grouped into 38 PCR ribotypes. Positivity rates per country varied (0-100%) and were at least 10% in 9/12 countries. No geographical clustering of samples with high positivity rates or in PCR ribotype distribution was observed. The most frequently detected PCR ribotypes (014/020, 078/126, 010 and 023) are also commonly reported in Europe among human clinically relevant isolates, in animal isolates and in the environment. Whole genome sequencing revealed several genetically related strain pairs (Spain/RT126, France/RT010, Austria and Sweden/RT276) and a cluster of very similar strains in RT078/126.ConclusionOur results suggest, the high potato contamination rates could have public health relevance. They indicate potatoes can serve as a vector for introducing C. difficile spores in the household environment, where the bacterium can then multiply in sensitive hosts with disrupted or unmature microbiota. Potato contamination with PCR ribotypes shared between humans, animals and soil is supportive of this view.

A point-prevalence study on community and inpatient Clostridioides difficile infections (CDI): results from Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI), July to November 2018.

BackgroundThere is a paucity of data on community-based Clostridioides difficile infection (CDI) and how these compare with inpatient CDI.AimTo compare data on the populations with CDI in hospitals vs the community across 12 European countries.MethodsFor this point-prevalence study (July-November 2018), testing sites sent residual diagnostic material on sampling days to a coordinating laboratory for CDI testing and PCR ribotyping (n = 3,163). Information on whether CDI testing was requested at the original site was used to identify undiagnosed CDI. We used medical records to identify differences between healthcare settings in patient demographics and risk factors for detection of C. difficile with or without free toxin.ResultsThe CDI positivity rate was 4.4% (country range: 0-16.2) in hospital samples, and 1.3% (country range: 0-2.2%) in community samples. The highest prevalence of toxinotype IIIb (027, 181 and 176) was seen in eastern European countries (56%; 43/77), the region with the lowest testing rate (58%; 164/281). Different predisposing risk factors were observed (use of broad-spectrum penicillins in the community (OR: 8.09 (1.9-35.6), p = 0.01); fluoroquinolones/cephalosporins in hospitals (OR: 2.2 (1.2-4.3), p = 0.01; OR: 2.0 (1.1-3.7), p = 0.02)). Half of community CDI cases were undetected because of absence of clinical suspicion, accounting for three times more undiagnosed adults in the community compared with hospitals (ca 111,000 vs 37,000 cases/year in Europe).ConclusionThese findings support recommendations for improving diagnosis in patients presenting with diarrhoea in the community, to guide good practice to limit the spread of CDI.

A purakau analysis of institutional barriers facing Maori occupational therapy students.

INTRODUCTION: Across Aotearoa (New Zealand), there are chronic shortages of qualified Maori (Indigenous peoples of Aotearoa) health practitioners and systemic ethnic health inequities. This study, focussing on the discipline of occupational therapy, explores Maori graduates' recollections of the institutional barriers that impacted on their study in this field over a 25-year period. METHODS: This qualitative study interviewed seven Maori occupational therapy graduates using purakau-an innovative Maori narrative inquiry method. Purakau (stories) were collected in 2018 via kanohi ki te kanohi (face to face) semi-structured interviews. They were analysed using the kaupapa Maori (Maori philosophical) framework of Pu-Ra-Ka-U which draws on traditional Maori matauranga (knowledge). FINDINGS: The institutional barriers identified were (1) cultural dissonance, (2) cultural (in)competency and (3) the limitations of (Western) pastoral care. CONCLUSION: This study highlighted how racism is embedded within the Western tertiary education system. To create a safe learning environment for Maori students, tertiary education institutions require a planned approach to address racism within policy, procedures, the curriculum, teaching and professional staff.

Eravacycline, a novel tetracycline derivative, does not induce Clostridioides difficile infection in an in vitro human gut model.

OBJECTIVES: The approval of new antibiotics is essential to combat infections caused by antimicrobial-resistant pathogens; however, such agents should be tested to determine their effect on the resident microbiota and propensity to select for opportunistic pathogens, such as Clostridioides difficile. Eravacycline is a new antibiotic for the treatment of complicated intra-abdominal infections. Here, we determined the effects of eravacycline compared with moxifloxacin on the microbiota and if these were conducive to induction of C. difficile infection (CDI). METHODS: We seeded in vitro chemostat models, which simulate the physiological conditions of the human colon, with a human faecal slurry and instilled gut-reflective concentrations of either eravacycline or moxifloxacin. RESULTS: Eravacycline instillation was associated with decreased Bifidobacterium, Lactobacillus and Clostridium species, which recovered 1 week after exposure. However, Bacteroides spp. levels decreased to below the limit of detection and did not recover prior to the end of the experiment. Post-eravacycline, a bloom of aerobic bacterial species occurred, including Enterobacteriaceae, compared with pre-antibiotic, which remained high for the duration of the experiment. These changes in microbiota were not associated with induction of CDI, as we observed a lack of C. difficile spore germination and thus no toxin was detected. Moxifloxacin exposure sufficiently disrupted the microbiota to induce simulated CDI, where C. difficile spore germination, outgrowth and toxin production were seen. CONCLUSIONS: These model data suggest that, despite the initial impact of eravacycline on the intestinal microbiota, similar to clinical trial data, this novel tetracycline has a low propensity to induce CDI.

The use of first-generation cephalosporin antibiotics, cefalexin and cefradine, is not associated with induction of simulated Clostridioides difficile infection.

OBJECTIVES: The use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections. Here, the effects of two first-generation cephalosporins, compared with a third-generation cephalosporin, on the human microbiota were investigated and their propensity to induce simulated CDI. METHODS: Three in vitro chemostat models, which simulate the physiochemical conditions of the human colon, were seeded with a human faecal slurry and instilled with either narrow-spectrum cephalosporins, cefalexin and cefradine, or a broad-spectrum cephalosporin, ceftriaxone, at concentrations reflective of colonic levels. RESULTS: Instillation of cefalexin was associated with reduced recoveries of Bifidobacterium and Enterobacteriaceae; however, Clostridium spp. recoveries remained unaffected. Cefradine exposure was associated with decreased recoveries of Bifidobacterium spp., Bacteroides spp. and Enterobacteriaceae. These changes were not associated with induction of CDI, as we observed a lack of C. difficile spore germination/proliferation, thus no toxin was detected. This is in contrast to a model exposed to ceftriaxone, where CDI was observed. CONCLUSIONS: These model data suggest that the minimal impact of first-generation cephalosporins, namely cefalexin and cefradine, on the intestinal microbiota results in a low propensity to induce CDI.

A survey of obstetricians' attitudes to induction of labour at 39 weeks gestation with the intention of reducing caesarean section rates.

BACKGROUND: Induction of labour (IOL) and caesarean section (CS) rates continue to increase in Australia, New Zealand and globally. There is evidence that CS rates are decreased in the context of medically indicated and elective IOL; therefore, the emerging concept of using IOL as means of preventing CS warrants investigation. AIMS: To assess obstetricians' opinions of elective IOL at 39 weeks gestation, its feasibility, generalisability and utility as a means of preventing CS in Australia and New Zealand. MATERIALS AND METHODS: A de-identified cross-sectional survey was distributed electronically to all Fellows and trainees of The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). The survey was voluntary and distributed with the approval of the RANZCOG Continuing Education Committee. The survey addressed opinions relating to rates of and indications for IOL, the perceived validity of those indications and explored the acceptability of using a screening tool to predict women at increased risk of intra-partum CS and tailoring obstetric management to include the option of IOL at 39 weeks gestation. RESULTS: The overall response rate was 34% (492/1423) (including trainees) and the response rate was 53% (394/750) for currently practising obstetricians. The majority (90%) of responders agreed on medical and clinical indications for IOL. There was no consensus on the validity of IOL if a woman were at apparent high risk of intra-partum CS; however, 81% (360/443) of clinicians would be interested in a tool that could predict those women at risk. CONCLUSIONS: There is heterogeneity of obstetrician's beliefs on using IOL at 39 weeks as a mechanism to reduce the CS rate.

Factors affecting reported Clostridioides difficile infection rates; the more you look the more you find, but should you believe what you see?

Reported rates of C. difficile infection (CDI) have increased in many settings; however, these can be affected by factors including testing density (test-density) and diagnostic methods. We aimed to describe the impact of multiple factors on CDI rates. Hospitals (n = 182) across five countries (France, Germany, Italy, Spain, and UK) provided data on; size and type of institution, CDI testing methodology, number of tests/month and patient-bed-days (pbds)/month over one year. Incidence rates were compared between countries, different sized institutions, types of institutions and testing method. After univariate analyses, the highest CDI rates were observed in Italy (average 11.8/10,000pbds/hospital/month), acute/primary hospitals (12.3/10,000pbds/hospital/month), small hospitals (16.7/10,000pbds/hospital/month), and hospitals using methods that do not detect toxin (NO-TOXIN) (e.g. GDH/NAAT or standalone NAAT) (10.7/10,000pbds/hospital/month). After adjusting for test-density, highest incidence rates were still in Italy, acute/primary hospitals and those using NO-TOXIN. The relative rate in long-term healthcare facilities (LTHCFs) increased, but size of institution no longer influenced the CDI rate. Test-density appears to have the largest effect on reported CDI rates. NO-TOXIN testing still influences CDI rates, even after adjusting for test-density, which is consistent with tests that 'overcall' true CDI. Low test-density can mask the true burden of CDI, e.g. in LTHCFs, highlighting the importance of good quality surveillance.

Female genital mutilation: Obstetric outcomes in metropolitan Sydney.

BACKGROUND: Female genital mutilation (FGM) and its impact on women's health are becoming relevant in Australia due to increases in numbers of refugees and migrants from affected countries. Notwithstanding the psychological trauma from FGM, there is a broad range of sequelae relevant to obstetrics and gynaecology, particularly related to maternal morbidity from labour and delivery. AIMS: To assess the prevalence of FGM in our unit and document its effect on maternal and neonatal outcomes. METHODS: Retrospective cohort study of women affected by FGM who delivered at a metropolitan hospital in Sydney over a five-year period. The primary outcome was mode of delivery and secondary outcomes addressed maternal morbidity and neonatal nursery admission compared with women unaffected by FGM. RESULTS: A full data set was available for 141/142 women affected by FGM. The overall prevalence of FGM was 1.64%. The majority of women affected by FGM were documented to have FGM 3 (41.1%). There was no difference in caesarean section rate. Women with FGM were less likely to be delivered by vacuum or forceps (11.1% vs 2.8%; P = 0.0009). There was no difference in perineal trauma, postpartum haemorrhage and neonatal nursery admission. Women with FGM 3 were more likely to have an episiotomy (4.8% vs 25.9%; P = 0.0007) without an increase in anal sphincter injury (P = 0.7). Documentation complying with local policy and guidelines was poor. CONCLUSIONS: FGM is increasingly common in Australia. This study adds to the Australian literature quantifying the effects on obstetric outcomes in these high-risk women.

Delivery in the second stage in theatre: Does consultant presence make a difference? A pilot study.

Complex operative obstetrics encompasses a range of clinical acumen, decision-making and surgical skill requiring training, supervision and practise. A period of mandated consultant presence in theatre in the second stage was prospectively audited at our institution to assess the impact of improved senior supervision on mode of delivery and maternal and neonatal morbidity.

Two Distinct Patterns of Clostridium difficile Diversity Across Europe Indicating Contrasting Routes of Spread.

Background: Rates of Clostridium difficile infection vary widely across Europe, as do prevalent ribotypes. The extent of Europe-wide diversity within each ribotype, however, is unknown. Methods: Inpatient diarrheal fecal samples submitted on a single day in summer and winter (2012-2013) to laboratories in 482 European hospitals were cultured for C. difficile, and isolates the 10 most prevalent ribotypes were whole-genome sequenced. Within each ribotype, country-based sequence clustering was assessed using the ratio of the median number of single-nucleotide polymorphisms between isolates within versus across different countries, using permutation tests. Time-scaled Bayesian phylogenies were used to reconstruct the historical location of each lineage. Results: Sequenced isolates (n = 624) were from 19 countries. Five ribotypes had within-country clustering: ribotype 356, only in Italy; ribotype 018, predominantly in Italy; ribotype 176, with distinct Czech and German clades; ribotype 001/072, including distinct German, Slovakian, and Spanish clades; and ribotype 027, with multiple predominantly country-specific clades including in Hungary, Italy, Germany, Romania, and Poland. By contrast, we found no within-country clustering for ribotypes 078, 015, 002, 014, and 020, consistent with a Europe-wide distribution. Fluoroquinolone resistance was significantly more common in within-country clustered ribotypes (P = .009). Fluoroquinolone-resistant isolates were also more tightly clustered geographically with a median (interquartile range) of 43 (0-213) miles between each isolate and the most closely genetically related isolate, versus 421 (204-680) miles in nonresistant pairs (P < .001). Conclusions: Two distinct patterns of C. difficile ribotype spread were observed, consistent with either predominantly healthcare-associated acquisition or Europe-wide dissemination via other routes/sources, for example, the food chain.

Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013.

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), the largest C. difficile epidemiological study of its type, PCR ribotype distribution of C. difficile isolates in Europe was investigated. PCR ribotyping was performed on 1,196 C. difficile isolates from diarrhoeal samples sent to the European coordinating laboratory in 2012-13 and 2013 (from two sampling days) by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (19%, n =222), 001/072 (11%, n = 134) and 014/020 (10%, n = 119) were the most prevalent. Distinct regional patterns of ribotype distribution were noted. Of 596 isolates from patients with toxin-positive stools (CDI cases), ribotype 027 accounted for 22% (32/144) of infections in cases aged from 18 to less than 65 years, but the prevalence decreased in those aged ≥ 65 years (14% (59/412)) and further decreased in those aged ≥ 81 years (9% (18/195)). The prevalence of ribotype 027 and 176, but not other epidemic strains, was inversely proportional to overall ribotype diversity (R(2) = 0.717). This study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable intercountry variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficile.

Caesarean section at full cervical dilatation.

BACKGROUND: Caesarean section at full cervical dilatation has many implications for maternal and neonatal morbidity as well as subsequent pregnancy outcomes. However, increasing trends are reported internationally for second-stage caesarean delivery. OBJECTIVES: To review the rate and indication for a caesarean section at full dilatation over a 5-year period at a tertiary referral obstetric centre in Sydney. MATERIALS AND METHODS: Retrospective cohort review of all women with a singleton, cephalic presenting fetus at ≥37(0)  weeks' gestation delivered by caesarean section in the second stage of labour between 1 January 2009 and 31 December 2013 at Royal Prince Alfred Hospital. Medical records were reviewed, and demographic, maternal and fetal outcome data were obtained. Consultant supervision and documentation standards were recorded. The main outcome measures were the rate of caesarean section at full cervical dilatation, maternal and fetal morbidity. RESULTS: During the study period, 8449/26063 (32.4%) babies were born by caesarean section. Of these surgical births, 476 (5.6%) were performed at full cervical dilatation at >37 weeks' gestation. There was no observed trend over the 5 years. The majority of women delivered by caesarean section at full dilatation were nulliparous and in spontaneous labour. More than half of these women were delivered without a trial of instrumental delivery. Consultant obstetricians were present for 7% of public second-stage caesarean deliveries. CONCLUSION: We report a 5-year experience with caesarean delivery at full dilatation at a tertiary unit. The rate was variable over the 5 years. Secondary outcome measures suggest that consultant supervision is uncommon and documentation standards require improvement.

Exploring the impact of the COVID-19 pandemic on perceptions of national scheduled childhood vaccines among Maori and Pacific caregivers, whanau, and healthcare professionals in Aotearoa New Zealand.

In Aotearoa New Zealand, there has been a marked decrease in the uptake of routine childhood vaccinations since the onset of the COVID-19 pandemic, particularly among Maori and Pacific children. This Maori and Pacific-centered research used an interpretive description methodology. We undertook culturally informed interviews and discussions with Maori and Pacific caregivers (n = 24) and healthcare professionals (n = 13) to understand their perceptions of routine childhood vaccines. Data were analyzed using reflexive thematic analysis and privileged respective Maori and Pacific worldviews. Four themes were constructed. "We go with the norm" reflected how social norms, health personnel and institutions promoted (and sometimes coerced) participants' acceptance of routine vaccines before the pandemic. "Everything became difficult" explains how the pandemic added challenges to the daily struggles of whanau (extended family networks) and healthcare professionals. Participants noted how information sources influenced disease and vaccine perceptions and health behaviors. "It needed to have an ethnic-specific approach" highlighted the inappropriateness of Western-centric strategies that dominated during the initial pandemic response that did not meet the needs of Maori and Pacific communities. Participants advocated for whanau-centric vaccination efforts. "People are now finding their voice" expressed renewed agency among whanau about vaccination following the immense pressure to receive COVID-19 vaccines. The pandemic created an opportune time to support informed parental vaccine decision-making in a manner that enhances the mana (authority, control) of whanau. Maori and Pacific-led vaccination strategies should be embedded in immunization service delivery to improve uptake and immunization experiences for whanau.

Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis.

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.

Counting (green) jobs in Queensland's waste and recycling sector.

The waste and recycling sector has been identified as a green industry and, as such, jobs within this sector may be classed as 'green jobs'. Many governments have seen green jobs as a way of increasing employment, particularly during the global financial crisis. However, the methods used to define and quantify green jobs directly affect the quantification of these green jobs. In December 2010, Queensland introduced a waste strategy that stated intent to increase green jobs within the waste sector. This article discusses the milieu and existing issues associated with quantifying green jobs within Queensland's waste and recycling sector, and provides a review of the survey that has sought to quantify the true size of the Queensland industry sector. This research has identified nearly 5500 jobs in Queensland's private waste management and recycling sector, which indicates that official data do not accurately reflect the true size of the sector.

Clostridioides difficile infection (CDI): A pan-European multi-center cost and resource utilization study, results from the Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

OBJECTIVES: Clostridioides difficile infection (CDI) is one of the leading nosocomial infections worldwide, resulting in a significantly increasing burden on the healthcare systems. However, Pan-European data about cost and resource utilization of CDI treatment do not exist. METHODS: A retrospective analysis within the Combatting Bacterial Resistance in Europe CDI project was conducted based on resource costs for inpatient treatment and productivity costs. Country-specific cost values were converted to EURO referred to 1 January, 2019 values. Differences in price levels for healthcare services among the participating countries were adjusted by using an international approach of the Organisation for Economic Co-operation and Development. As the study focused on patients with recurrent CDI, the observed study population was categorized into (a) patients with CDI but without CDI recurrence (case group), (b) patients with CDI recurrence (recurrence group), and (c) patients without CDI (control group). RESULTS: Overall, 430 hospitalized patients from 12 European countries were included into the analysis between July 2018 and November 2018. Distribution of mean hospital length of stay and mean overall costs per patient between the case group, recurrence group, and control group were as follows: 22 days (95% CI 17-27 days) vs. 55 days (95% CI 17-94 days) vs. 26 days (95% CI 22-31 days; p 0.008) and € 15 242 (95% CI 10 593-19 891) vs. € 52 024 (95% CI 715-103 334) vs. € 21 759 (95% CI 16 484-27 035; p 0.010), respectively. The CDI recurrence rate during the observational period was 18%. Change escalation in CDI medication (OR 3.735) and treatment in an intensive care unit (OR 5.454) were found to be the most important variables associated with increased overall costs of patients with CDI. CONCLUSIONS: Treatment of patients with recurrent CDI results in a significant burden. Prevention of CDI recurrences should be in focus of daily patient care to identify the most cost-effective treatment strategy.

Impact of testing on Clostridioides difficile infection in hospitals across Europe: a mathematical model.

OBJECTIVES: The prevalence of Clostridioides difficile infection (CDI) has been shown to vary markedly between European countries, both in hospitals and in the community. Determining the true prevalence has proven challenging. Without systematic testing in hospitals, the unchecked transmission of CDI can lead to large outbreaks in more susceptible cohorts. We investigate the success of CDI surveillance and control measures across Europe, by examining the dynamics of disease spread from the community into a hospital setting. We focus on national differences, such as variability in testing and sampling, disease prevalence in communities and hospitals, and antimicrobial usage. METHODS: We developed a stochastic, compartmental, dynamic mathematical model parameterized using sampling and testing rate data from COMBACTE-CDI, a multicountry study in which all diarrhoeal stool samples (N = 3163) from European laboratories were tested for CDI, and data for antimicrobial usage and incidence of hospital cases sourced from the European Centre for Disease Prevention and Control. RESULTS: The framework estimates the prevalence of CDI among hospital patients across European countries and explores how national differences impact the dynamics, transmission, and relative incidence of CDI within the hospital setting. The model illustrates the mechanisms influencing these national differences, namely, antimicrobial usage rates, national sampling and testing rates, and community prevalence of CDI. DISCUSSION: Differential costs for testing and practicalities of scaling up testing mean every country needs to consider balancing CDI testing costs against the costs of treatment and care of patients with CDI.

A network meta-analysis of psychological interventions for schizophrenia and psychosis: Impact on symptoms.

BACKGROUND: Evidence for the effectiveness of psychological interventions for schizophrenia/psychosis is growing, however there is no consensus on the psychological intervention most likely to reduce symptoms. METHODS: A network meta-analysis was conducted to identify all randomised controlled trials (RCTs) of psychological interventions for adults with schizophrenia/psychosis. A systematic review of the literature using MEDLINE, PsycINFO, EMBASE and CENTRAL led to an analysis of 90 RCTs with 8440 randomised participants across 24 psychological intervention, and control groups. Psychological interventions were categorised and rated for treatment fidelity and risk of bias. Data for total symptoms were extracted and network meta-analysis, using a frequentist approach, was undertaken using Stata SE v15 to compare the direct and indirect evidence for the effectiveness of each psychological intervention. FINDINGS: Psychological interventions were more likely to reduce symptoms than control groups, and one intervention, mindfulness-based psychoeducation, was consistently ranked as most likely to reduce total symptoms. Subgroup analyses identified differential effectiveness in different settings and for different subgroups. INTERPRETATION: Mindfulness-based psychoeducation was consistently ranked as most likely to reduce symptoms; however all studies were based in China. More RCTs in a variety of cultural contexts would help to elucidate whether these findings generalise internationally. A number of psychological interventions could potentially be more effective than interventions recommended by NICE guidelines, such as CBT and family therapy, and additional RCTs and meta-analyses are needed to generate more conclusive evidence in this regard.

Trehalose-Induced Remodelling of the Human Microbiota Affects Clostridioides difficile Infection Outcome in an In Vitro Colonic Model: A Pilot Study.

Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including Clostridioides difficile. Trehalose has been reported to enhance virulence of certain C. difficile ribotypes; however, such variants are widespread and not correlated with clinical outcomes for patients suffering from C. difficile infection (CDI). Here, we make preliminary observations on how trehalose supplementation affects the microbiota in an in vitro model and show that trehalose-induced changes can reduce the outgrowth of C. difficile, preventing simulated CDI. Three clinically reflective human gut models simulated the effects of sugar (trehalose or glucose) or saline ingestion on the microbiota. Models were instilled with sugar or saline and further exposed to C. difficile spores. The recovery of the microbiota following antibiotic treatment and CDI induction was monitored in each model. The human microbiota remodelled to utilise the bioavailable trehalose. Clindamycin induction caused simulated CDI in models supplemented with either glucose or saline; however, trehalose supplementation did not result in CDI, although limited spore germination did occur. The absence of CDI in trehalose model was associated with enhanced abundances of Finegoldia, Faecalibacterium and Oscillospira, and reduced abundances of Klebsiella and Clostridium spp., compared with the other models. Functional analysis of the microbiota in the trehalose model revealed differences in the metabolic pathways, such as amino acid metabolism, which could be attributed to prevention of CDI. Our data show that trehalose supplementation remodelled the microbiota, which prevented simulated CDI, potentially due to enhanced recovery of nutritionally competitive microbiota against C. difficile.