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2.
J Exp Med ; 221(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38563820

RESUMO

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.


Assuntos
Colite , Dermatite , Hipersensibilidade , Humanos , Autoimunidade , Colite/genética , Inflamação , Janus Quinase 1/genética
3.
Hum Vaccin Immunother ; 20(1): 2301626, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38205779

RESUMO

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.


Assuntos
COVID-19 , Cuidadores , Vacinação , Criança , Humanos , Atenção à Saúde , Pessoal de Saúde , Povo Maori , Nova Zelândia/epidemiologia , Pandemias , População das Ilhas do Pacífico , Vacinação/estatística & dados numéricos , Assistência à Saúde Culturalmente Competente , Programas de Imunização
4.
J Biol Chem ; 300(1): 105529, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043796

RESUMO

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.


Assuntos
Proteínas de Bactérias , Clostridioides difficile , Peptidoglicano , Peptidil Transferases , Proteínas de Bactérias/química , Resistência beta-Lactâmica , beta-Lactamas/farmacologia , Catálise , Clostridioides difficile/enzimologia , Clostridioides difficile/genética , Peptidoglicano/química , Peptidil Transferases/química , Peptidil Transferases/genética
5.
Clin Microbiol Infect ; 29(6): 796.e1-796.e6, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36773769

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Humanos , Europa (Continente)/epidemiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Hospitais , Modelos Teóricos , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia
6.
Clin Microbiol Infect ; 29(5): 651.e1-651.e8, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36586512

RESUMO

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.


Assuntos
Infecções por Clostridium , Hospitalização , Humanos , Estudos Retrospectivos , Custos de Cuidados de Saúde , Infecções por Clostridium/microbiologia , Europa (Continente) , Recidiva
7.
Euro Surveill ; 27(26)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35775426

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Adulto , Clostridioides difficile/genética , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Estudos Transversais , Europa (Continente)/epidemiologia , Humanos , Pacientes Internados , Prevalência , Ribotipagem
8.
Aust Occup Ther J ; 69(4): 414-423, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35383408

RESUMO

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.


Assuntos
Havaiano Nativo ou Outro Ilhéu do Pacífico , Terapia Ocupacional , Humanos , Narração , Nova Zelândia , Pesquisa Qualitativa , Estudantes
9.
Euro Surveill ; 27(15)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35426363

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Solanum tuberosum , Animais , Clostridioides , Clostridioides difficile/genética , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Europa (Continente)/epidemiologia , Humanos , Reação em Cadeia da Polimerase , Ribotipagem , Solanum tuberosum/genética
10.
J Antimicrob Chemother ; 77(1): 148-154, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561709

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Antibacterianos/farmacologia , Cefalexina , Cefalosporinas/efeitos adversos , Cefradina , Infecções por Clostridium/microbiologia , Humanos
11.
Front Cell Infect Microbiol ; 11: 670935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277467

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Microbiota , Antibacterianos/uso terapêutico , Clostridioides , Infecções por Clostridium/tratamento farmacológico , Humanos , Projetos Piloto , Trealose
12.
Schizophr Res ; 228: 447-459, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33578368

RESUMO

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.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Adulto , China , Humanos , Metanálise em Rede , Intervenção Psicossocial , Psicoterapia , Transtornos Psicóticos/terapia , Esquizofrenia/terapia
13.
NPJ Biofilms Microbiomes ; 7(1): 16, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547298

RESUMO

C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing a burden on healthcare systems and increasing patient morbidity. We have little understanding of why these therapies fail. Here, we use a clinically validated in vitro gut model to assess the contribution of biofilms towards recurrent disease and to investigate biofilm microbiota-C. difficile interactions. Initial experiments show that C. difficile cells became associated with the colonic biofilm microbiota and are not depleted by vancomycin or faecal microbiota transplant therapies. We observe that transferring biofilm encased C. difficile cells into a C. difficile naïve but CDI susceptible model induces CDI. Members of the biofilm community can impact C. difficile biofilm formation by acting either antagonistically or synergistically. We highlight the importance of biofilms as a reservoir for C. difficile, which can be a cause for recurrent infections.


Assuntos
Biofilmes/crescimento & desenvolvimento , Clostridioides difficile/patogenicidade , Infecções por Clostridium/microbiologia , Colo/microbiologia , Idoso , Idoso de 80 Anos ou mais , Técnicas Bacteriológicas , Biofilmes/efeitos dos fármacos , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Colo/efeitos dos fármacos , Transplante de Microbiota Fecal , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Reinfecção/tratamento farmacológico , Reinfecção/microbiologia , Vancomicina/farmacologia
14.
Aust N Z J Obstet Gynaecol ; 61(1): 94-99, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32985691

RESUMO

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.


Assuntos
Cesárea , Intenção , Trabalho de Parto Induzido , Atitude , Austrália , Estudos Transversais , Feminino , Humanos , Nova Zelândia , Gravidez
15.
J Antimicrob Chemother ; 76(1): 171-178, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32929459

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clostridioides , Infecções por Clostridium/tratamento farmacológico , Humanos , Tetraciclinas
16.
Front Public Health ; 8: 293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766196

RESUMO

Background: There are inconsistent data on the risk factors for Clostridium difficile infection (CDI) in the literature. Aims: To use two C. difficile infection (CDI) case-control study groups to compare risk factors in hospitalized patients with diarrhea across different countries. Methods: A multi-center group of CDI cases/controls were identified by standardized testing from seven countries from the prior EUropean, multi-center, prospective bi-annual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhea (EUCLID). A second group of CDI cases/controls was identified from a single center in Germany [parallel study site (PSS)]. Data were extracted from the medical notes to assess CDI risk factors. Univariate analyses and multivariate logistic regression models were used to identify and compare risk factors between the two groups. Results: There were 253 and 158 cases and 921 and 584 controls in the PSS and EUCLID groups, respectively. Significant variables from univariate analyses in both groups were age ≥65, number of antibiotics (OR 1.2 for each additional antibiotic) and prior hospital admission (all p < 0.001). Congestive heart failure, diabetes, admission from assisted living or Emergency Department, proton pump inhibitors, and chronic renal disease were significant in PSS (all p < 0.05) but not EUCLID. Dementia and admitted with other bacterial diseases were significant in EUCLID (p < 0.05) but not PSS. Following multivariate analyses, age ≥ 65, number of antibiotics and prior hospital admission were consistently identified as CDI risk factors in each individual group and combined datasets. Conclusion: Our results show that the same CDI risk factors were identified across datasets. These were age ≥ 65 years, antibiotic use and prior hospital admission. Importantly, the odds of developing CDI increases with each extra antibiotic prescribed.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Idoso , Estudos de Casos e Controles , Infecções por Clostridium/epidemiologia , Diarreia/epidemiologia , Alemanha/epidemiologia , Humanos , Estudos Prospectivos , Fatores de Risco
17.
Anaerobe ; 62: 102178, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32092415

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/diagnóstico , Infecção Hospitalar/epidemiologia , Análise Fatorial , França , Alemanha , Instalações de Saúde , Hospitais , Humanos , Itália , Espanha
18.
J Vet Intern Med ; 34(2): 922-932, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32009244

RESUMO

BACKGROUND: Transportation has been suggested as a risk factor for gastric ulceration in horses, but limited evidence supports this assumption. ANIMALS: Twenty-six Standardbred, Thoroughbred, and Warmblood mares from a university teaching herd. METHODS: Twelve mares were confined for 12 hours, overnight, in reproductive stocks with indwelling nasogastric tubes (NGTs) to assess pH of gastric fluid (GF). Gastric ulceration was assessed endoscopically before and after confinement. Subsequently, 26 horses were transported for 12 hours, overnight, in 2 consignments. During transportation, GF was aspirated from indwelling NGT placed in the same 12 mares used in the confinement study, and gastric ulceration was assessed endoscopically before and after transportation in all horses. RESULTS: The median pH of GF in confined horses was 1.70-2.49 at each sampling point, and there was no apparent effect on gastric squamous ulcer scores. The median pH of GF from the same 12 horses at corresponding sampling times during transportation was 6.82-7.22. Transportation was associated with increased gastric squamous ulcer scores, particularly in horses fasted for gastroscopy and NGT placement immediately before departure. Gastric emptying appeared delayed after transportation in horses fed before departure. CONCLUSIONS AND CLINICAL IMPORTANCE: Transportation is associated with increased gastric squamous ulceration and with increased pH of GF. These findings may be a consequence of impaired gastric emptying and reflux of alkaline small intestinal content, with factors such as duodenal bile salts and short-chain fatty acids mediating mucosal injury.


Assuntos
Conteúdo Gastrointestinal/química , Doenças dos Cavalos/fisiopatologia , Úlcera Gástrica/veterinária , Meios de Transporte , Animais , Feminino , Cavalos , Concentração de Íons de Hidrogênio , Úlcera Gástrica/fisiopatologia
19.
Aust N Z J Obstet Gynaecol ; 59(5): 730-733, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31270816

RESUMO

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.


Assuntos
Cesárea/estatística & dados numéricos , Consultores , Tomada de Decisões , Segunda Fase do Trabalho de Parto , Avaliação de Resultados em Cuidados de Saúde , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Auditoria Médica , New South Wales , Projetos Piloto , Gravidez , Resultado da Gravidez , Estudos Prospectivos
20.
Aust N Z J Obstet Gynaecol ; 59(2): 312-316, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30734267

RESUMO

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.


Assuntos
Circuncisão Feminina/efeitos adversos , Complicações do Trabalho de Parto/epidemiologia , Adulto , Austrália , Circuncisão Feminina/estatística & dados numéricos , Parto Obstétrico , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Humanos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Adulto Jovem
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