10957 research outputs found
Sort by
Quantitative Polymerase Chain Reaction Identified a Multitude of mcr-1 to mcr-5 Genes in Fresh Cow Dung in Bangladesh: An Urgent Public Health Concern
No full textIntroduction:
The emergence of antimicrobial resistance (AMR) in the food industry is a serious global public health threat. Colistin is frequently used as a growth promoter in livestock, which is a concern. The widespread use of colistin in the food industry is linked to the emergence of mobilised colistin resistance (mcr) genes. This must be avoided with colistin, an important Reserve antibiotic in humans. Consequently, there is an urgent need to investigate current variants of mcr gene in cattle faeces in Bangladesh.
Methods:
Cross-sectional study analysing mcr-1 to mcr-5 in fresh cow dung samples from 20 commercial farms and 6 individual houses. DNA was extracted from cow dung samples using commercial kits. Real-time quantitative polymerase chain reaction was used to assess the five mcr genes in the extracted DNA.
Results:
40.8% (49/120) of the samples revealed the existence of at least one mcr gene, with mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 identified in 27.5% (33/120), 2.5% (3/120), 4.2% (5/120), 14.2% (17/120) and 8.3% (10/120) of samples, respectively. Co-occurrence of two or more genes was documented in 8.3% samples, with co-carriage of three genes in 1.7% of samples. No significantly higher numbers of mcr genes were identified between commercial farms and individual households.
Conclusion:
Excess use of antibiotics in cattle may result in increased prevalence of antibiotic-resistant genes. A comprehensive One Health approach is urgently needed in Bangladesh to reduce the spread of colistin resistance and meet the United Nation’s targets for Access to antibiotics and AMR
Comparative performance of a commercial and in-house Mp1p antigen-detecting enzyme immunoassay for the rapid diagnosis of talaromycosis
Get PDFBackground
Several antigen-detection assays have been developed for the rapid diagnosis of talaromycosis, but their utility has been limited by a lack of commercial options. The aim of this study was to perform a head-to-head comparison of the performance of our in-house monoclonal antibody-based Mp1p antigen-detecting enzyme immunoassay (EIA) with its recently-developed commercial platform.
Methods
In this diagnostic accuracy, retrospective, case-cohort study, we compared the sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of the commercial Wantai Mp1p EIA versus our in-house Mp1p EIA on paired plasma and urine samples from 424 hospitalized adults with advanced HIV disease, including 224 cases of proven talaromycosis, where Talaromyces marneffei was isolated in culture of blood or other clinical specimens, and 200 controls diagnosed with a range of other opportunistic infections. All participants were randomly selected from prospective cohorts recruited between 2011 and 2019 from five centers in Vietnam.
Results
The sensitivity of the Wantai and in-house Mp1p EIAs were comparable in plasma (95.1% vs 92.4%, P = 0.11), in urine (91.5% vs 87.1% P = 0.07), and in combined testing of plasma and urine (96.4% vs 96.0%, P = 1.00), where talaromycosis was diagnosed based on the positivity of either specimen. The specificity of the Wantai and in-house Mp1p EIAs were consistently high in plasma, in urine, and in combined testing (93 – 97%). The Wantai and in-house Mp1p EIAs provided substantially higher sensitivity than blood culture detection (96.4% and 96.0% vs 78.6%, P < 0.001). For both EIAs, LR+ were greater than 10 and LR- were less than 0.1, which increases the confidence to rule in or rule out talaromycosis.
Conclusions
The diagnostic performance of the Wantai Mp1p EIA was comparable to our validated in-house Mp1p EIA, and significantly more sensitive than blood culture, offering a standardized tool for the rapid diagnosis of talaromycosis
Culturally Tailored Diabetes Self-Management Education and Support Programs in Black African and Caribbean Adults With Type 2 Diabetes (HEAL-D): Protocol for a Multicenter, Pragmatic Randomized Controlled Trial
No full textBackground:
People of Black African and Black Caribbean ethnicity experience higher rates and poorer outcomes of type 2 diabetes (T2D) than people of White European ethnicity; these inequalities are compounded by poor healthcare access. Cultural tailoring of diabetes self-management education and support (DSMES) programs has the potential to improve healthcare engagement and clinical outcomes for ethnic minority groups. Healthy Eating & Active Lifestyles for Diabetes (HEAL-D) is a co-designed, culturally tailored group-based DSMES program for adults of Black African and Black Caribbean ethnicity.
Objective:
This trial aims to evaluate the clinical and cost effectiveness of the HEAL-D intervention, compared to standard DSMES programs, in Black African and Black Caribbean adults living with T2D.
Methods:
A 24-month, multicenter, pragmatic, open-label, 2-arm, parallel-group, individually randomized group treatment trial will be conducted, with primary end point (glycated hemoglobin [HbA1c]) assessment at 12 months. Black African and Black Caribbean adults with T2D (n=300), recruited from 3 to 5 centers in the United Kingdom (including London, West Midlands, and Greater Manchester), will be randomized in a 1:1 ratio to HEAL-D (intervention) or a standard DSMES program (control). HbA1c, blood lipids, anthropometric outcomes, blood pressure, physical activity, and patient-reported outcome measures relating to psychological well-being and self-management support, lifestyle behaviors, and health economics will be collected at baseline and follow-up visits (6, 12, and 24 months). Cost-effectiveness will be assessed through a cost-utility analysis conducted from a health and social care perspective. A mixed methods process evaluation will provide a formative evaluation of delivery, intervention fidelity, and implementation of HEAL-D, and an embedded study within a project will assess the impact of multiple long-term conditions on uptake of, and engagement with HEAL-D, and the impact of HEAL-D on multiple long-term conditions. The trial received Research Authority and Research Ethics Council approval on April 22, 2024.
Results:
Funding began in August 2023. Site “green light” was received on August 15, 2024, for London; November 29, 2024, for Manchester; and January 31, 2025, for the West Midlands. Recruitment commenced in August 2024 and is due to run for 11 months. As of March 26, 2025, a total of 76 participants have consented. Last patient, last visit is expected in June 2027; primary data analysis is expected to begin in July 2027. Final results are anticipated to be available in September 2027, and publication is expected by the end of 2027.
Conclusions:
The HEAL-D trial will address whether a culturally tailored DSMES program, provided in-person or via videoconferencing, is clinically and cost-effective compared to standard DSMES at improving diabetes management in Black African and Black Caribbean adults. If effective, this would provide an evidence-based model of equitable DSMES services and improve the implementation of healthcare programs for ethnic minority groups
Immunophenotyping of apparently immunocompetent hosts with cryptococcosis reveals IL-17 deficiency as a unifying susceptibility factor
Get PDFIntroduction
We describe the immunophenotyping and genetic analysis of HIV-uninfected apparently immunocompetent adults presenting with disseminated cryptococcosis. Cryptococci are environmentally ubiquitous fungi that may cause disseminated infection including meningitis. Cryptococcosis occurs predominantly in immunocompromised hosts and most commonly in the context of human immunodeficiency virus (HIV) infection. In apparently immunocompetent patients, cryptococcal disease is rare, often diagnosed later and associated with higher mortality. The immunologic work-up and management of this patient group is challenging and poorly studied.
Methods
Between 2015-2021, eight apparently immunocompetent adults at the time of diagnosis with cryptococcosis underwent extensive diagnostic immunological work-up including T-/B-cell subsets, immunoglobulins, T-cell proliferation and phenotyping, serum-specific antibody responses, mannose binding lectin, measurement of selected cytokines, anti-cytokine autoantibodies and targeted genetic next-generation sequencing.
Results
The production of interleukin (IL)-17 following phytohaemagglutinin (PHA) stimulation was significantly reduced in all eight patients with cryptococcosis compared to healthy controls (median IL-17 concentration in whole blood stimulation assay 88.1pg/mL in patients; 452.1pg/mL in controls, p=0.0047). In 5/5 patients tested, the percentage of CD4+ T-cells positive for IL-17, including memory CD4+CD45RO+ IL-17+ T-cells, after stimulation with staphylococcal enterotoxin B (SEB) was significantly reduced (&lt;=0.4% cells). Reduced IgM+ memory B-cells were noted in 4/5 tested. 4/8 patients were found to have CD4 lymphopaenia. One patient with Cryptococcus gattii infection had autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). No underlying genetic causes were identified.
Conclusion
Patients had several immunological risk factors, but reduced IL-17 production was a striking feature across the cohort – a phenotype that may facilitate tailored immunotherapeutic approaches
Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis
Get PDFPyrazinamide and isoniazid are first-line drugs for tuberculous meningitis (TBM), but limited information is available on their plasma pharmacokinetics, and particularly cerebrospinal fluid (CSF) penetration, in patients with TBM. Any potential effect of co-administration with high-dose rifampicin, also being evaluated in trials for TBM, is unknown. Understanding this is important for dose optimisation. We characterized pyrazinamide and isoniazid plasma and CSF pharmacokinetics among adults enrolled in a phase 2 clinical trial of intensified antibiotic therapy for HIV-associated TBM. Participants were randomized to receive either standard TBM treatment (including rifampicin 10 mg/kg) or high-dose rifampicin (35 mg/kg) plus linezolid, with or without aspirin. Plasma and lumbar CSF samples were collected on days 3 and 28 after study enrollment, and drug concentrations were measured using liquid chromatography-tandem mass spectrometry. Data were analysed using nonlinear mixed-effects modeling. Forty-nine participants provided 414 plasma and 44 CSF concentrations. Pyrazinamide CSF concentrations equilibrated with plasma with a half-life of 0.66 h and a pseudo-partition coefficient of 1.05. Isoniazid concentrations equilibrated with a half-life of 3.87 h and a pseudo-partition coefficient of 1.04. Pyrazinamide clearance increased by 30% from day 3 to day 28. NAT2 phenotype determined multi-modal isoniazid clearance. High-dose rifampicin did not affect pyrazinamide or isoniazid plasma pharmacokinetics or CSF penetration. Both drugs achieved exposure in CSF similar to plasma, supporting their crucial role in TBM treatment. Plasma pharmacokinetics of pyrazinamide and isoniazid in TBM were consistent with previously reported values in pulmonary tuberculosis, even when co-administered with high-dose rifampicin
Oral cholera vaccine uptake, acceptance and confidence among residents of a high-risk township in Zambia: key insights for future vaccination programs
No full textBackground
Oral cholera vaccines (OCVs) prevent cholera and save lives. Given the recent 2024 country-wide cholera epidemic in Zambia, we determined self-reported OCV uptake, acceptance and confidence among adults living in a high-risk, cholera-prone township in Zambia.
Methods
A descriptive cross-sectional study was conducted from April to August 2024, involving 385 randomly selected adult participants residing in the Kanyama township of Lusaka, Zambia. Data were collected using an interviewer-administered questionnaire and statistically analysed.
Results
Self-reported uptake of at least one dose of the OCV was 18%, with the majority (315 [82%]) reporting being unvaccinated against cholera. Among those who were unvaccinated, vaccine acceptance was <10% (95% confidence interval [CI] 6.8 to 13.7), with higher rates reported among women than men (p=0.002). Despite this, the majority (210 [84.3%]) expressed confidence in the vaccination program. Those knowledgeable about the OCV were twice as likely to get vaccinated (adjusted odds ratio 2.60 [95% CI 1.19 to 5.68]). Knowledge, attitudes and perceptions were associated with OCV uptake.
Conclusions
Self-reported OCV uptake and acceptance were low in a high-risk cholera-prone township in Zambia. Community education on the benefits of the vaccine is urgently needed to enhance confidence and attitudes towards the OCV and improve vaccination rates in the future
Antiarrhythmic drug use in atrial fibrillation among different European countries – as determined by a physician survey
Get PDFBackground
There is limited knowledge of physicians’ antiarrhythmic drug (AAD) treatment practices for patients with atrial fibrillation and adherence to guidelines in European countries.
Methods
An online survey (n = 321) of cardiologists, cardiac electrophysiologists and interventional electrophysiologists was conducted in Germany (DE; n = 83), Italy (IT; n = 95), Sweden (SE; n = 60) and the United Kingdom (UK; n = 83) including 96 questions on treatment practices.
Results
ESC guidelines were the most important non-patient factor influencing treatment practice (55–72 %). However, while amiodarone was frequently (88–93 %) used in heart failure with reduced left ventricular ejection fraction, it was also a typical treatment choice for minimal/no-structural heart disease (SHD) (28 %), particularly in UK. Other deviations from guidelines were the use of class 1C drugs in coronary artery disease (CAD) and other SHD, and use of sotalol in left ventricular hypertrophy and renal impairment. In-hospital initiation of sotalol was low, with the exception of SE. Sotalol (16–41 %) and dronedarone use (10–54 %) in CAD varied among countries. For frequent, symptomatic paroxysmal AF, ablation was generally favoured, but AADs were preferred by 53 % in SE. In asymptomatic or subclinical AF, AADs were used by 41 % (range: 22–60 %), ablation by 11 % (range 2–18 %). In contrast to guidelines that prioritize safety, anticipated efficacy was more important (51 %) than safety (31 %) when selecting AADs.
Conclusions
Despite recognizing the importance of guidelines, deviations in AAD use were common with the potential to compromise patient safety. These findings indicate the need for more educational support for optimal AAD selection in AF management
Cost Utility of Specialist Physiotherapy for Functional Motor Disorder (Physio4FMD)
Get PDFBackground and Objectives
Functional motor disorder (FMD), a motor-dominant variant of functional neurologic disorder, is a disabling condition associated with high health and social care resource use and poor employment outcomes. Specialist physiotherapy presents a possible treatment option, but there is limited evidence for clinical effectiveness and cost-effectiveness. Physio4FMD is a multicenter randomized controlled trial of specialist physiotherapy for FMD compared with treatment as usual (TAU). The aim of the analysis was to conduct a randomized trial based on economic evaluation of specialist physiotherapy compared with TAU.
Methods
Eleven centers in England and Scotland randomized participants 1:1 to specialist physiotherapy or TAU (referral to community neurologic physiotherapy). Participants completed the EuroQoL EQ-5D-5L, Client Service Receipt Inventory, and Work Productivity and Activity Impairment Questionnaire at baseline, 6 months, and 12 months. The mean incremental cost per quality-adjusted life year (QALY) for specialist physiotherapy compared with TAU over 12 months was calculated from a health and social care and wider societal perspective. The probability of cost-effectiveness and 95% CIs were calculated using bootstrapping.
Results
The analysis included 247 participants (n = 141 for specialist physiotherapy, n = 106 for TAU). The mean cost per participant for specialist physiotherapy was £646 (SD 72) compared with £272 (SD 374) for TAU. Including the costs of treatment, the adjusted mean health and social care cost per participant at 12 months for specialist physiotherapy was £3,814 (95% CI £3,194–£4,433) compared with £3,670 (95% CI £2,931–£4,410) for TAU, with a mean incremental cost of £143 (95% CI £–825 to £1,112). There was no significant difference in QALYs over the 12-month duration of the trial (0.030, 95% CI –0.007 to 0.067). The mean incremental cost per QALY was £4,133 with an 86% probability of being cost-effective at a £20,000 threshold. When broader societal costs such as loss of productivity were taken into consideration, specialist physiotherapy was dominant (incremental cost: £−5,169, 95% CI £–15,394 to £5,056).
Discussion
FMD was associated with high health and social care costs. There is a high probability that specialist physiotherapy is cost-effective compared with TAU particularly when wider societal costs are taken into account.
Trial Registration Information
International Standard Randomised Controlled Trial registry, ISRCTN56136713
Delivery of Biomolecules into Individual Cells and Subcellular Compartments by Localized Electroporation via Nanopipette
Get PDFIntroducing exogenous biomolecules into individual cells with precise control over space, time, and dosage is crucial for both fundamental and applied biological research. Glass nanopipettes have long been employed to deliver biomolecules into individual cells; yet, their reliance on the electrical charge of the target molecule and the need for penetrating the cellular membrane pose significant limitations. We demonstrate that voltage pulses applied through a glass nanopipette in proximity to the cell membrane induce localized electroporation and generate directional flow, enabling controlled delivery of both charged and neutral biomolecules into subcellular compartments, e.g., the nucleus, without the need for penetrating the cellular membrane. This approach minimizes cell damage and preserves cell viability, even after multiple rounds of injection. Our findings will serve as a reference for the design of novel nanopipette methods, contributing to the newly established field of spatiotemporal analysis of live cells
Access Repository Dashboard
Do you manage St George's Online Research Archive? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!