Imperial College London

ProfessorAlisonHolmes

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 3313 1283alison.holmes

 
 
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Location

 

8N16Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

441 results found

Riezk A, Wilson RC, Cass AEG, Holmes AH, Rawson TMet al., 2024, A low-volume LC/MS method for highly sensitive monitoring of phenoxymethylpenicillin, benzylpenicillin, and probenecid in human serum, Analytical Methods: advancing methods and applications, Vol: 16, Pages: 558-565, ISSN: 1759-9660

Background: The optimization of antimicrobial dosing plays a crucial role in improving the likelihood of achieving therapeutic success while reducing the risks associated with toxicity and antimicrobial resistance. Probenecid has shown significant potential in enhancing the serum exposure of phenoxymethylpenicillin, thereby allowing for lower doses of phenoxymethylpenicillin to achieve similar pharmacokinetic/pharmacodynamic (PK/PD) targets. We developed a triple quadrupole liquid chromatography mass spectrometry (TQ LC/MS) analysis of, phenoxymethylpenicillin, benzylpenicillin and probenecid using benzylpenicillin-d7 and probenecid-d14 as IS in single low-volumes of human serum, with improved limit of quantification to support therapeutic drug monitoring. Methods: Sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using TQ LC/MS. The mobile phase consisted of 55% methanol in water + 0.1% formic acid, with a flow rate of 0.4 mL min-1. Antibiotic stability was assessed at different temperatures. Results: Chromatographic separation was achieved within 2 minutes, allowing simultaneous measurement of phenoxymethylpenicillin, benzylpenicillin and probenecid in a single 15 μL blood sample. Validation indicated linearity over the range 0.0015-10 mg L-1, with accuracy of 96-102% and a LLOQ of 0.01 mg L-1. All drugs demonstrated good stability under different storage conditions. Conclusion: The developed method is simple, rapid, accurate and clinically applicable for the quantification of phenoxymethylpenicillin, benzylpenicillin and probenecid in tandem.

Journal article

Wan Y, Myall AC, Boonyasiri A, Bolt F, Ledda A, Mookerjee S, Wei├če AY, Getino M, Turton JF, Abbas H, Prakapaite R, Sabnis A, Abdolrasouli A, Malpartida-Cardenas K, Miglietta L, Donaldson H, Gilchrist M, Hopkins KL, Ellington MJ, Otter JA, Larrouy-Maumus G, Edwards AM, Rodriguez-Manzano J, Didelot X, Barahona M, Holmes AH, Jauneikaite E, Davies Fet al., 2024, Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes., J Infect Dis

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

Journal article

Bolton W, Wilson R, Gilchrist M, Georgiou P, Holmes A, Rawson Tet al., 2024, Personalising intravenous to oral antibiotic switch decision making through fair interpretable machine learning, Nature Communications, Vol: 15, ISSN: 2041-1723

Antimicrobial resistance (AMR) and healthcare associated infections pose a significant threat globally. One key prevention strategy is to follow antimicrobial stewardship practices, in particular, to maximise targeted oral therapy and reduce the use of indwelling vascular devices for intravenous (IV) administration. Appreciating when an individual patient can switch from IV to oral antibiotic treatment is often non-trivial and not standardised. To tackle this problem we created a machine learning model to predict when a patient could switch based on routinely collected clinical parameters. 10,362 unique intensive care unit stays were extracted and two informative feature sets identified. Our best model achieved a mean AUROC of 0.80 (SD 0.01) on the hold-out set while not being biased to individuals protected characteristics. Interpretability methodologies were employed to create clinically useful visual explanations. In summary, our model provides individualised, fair, and interpretable predictions for when a patient could switch from IV-to-oral antibiotic treatment. Prospectively evaluation of safety and efficacy is needed before such technology can be applied clinically.

Journal article

Bonaconsa C, Nampoothiri V, Mbamalu O, Dlamini S, Surendran S, Singh SK, Ahmad R, Holmes A, Rasheed MA, Mendelson M, Charani Eet al., 2024, Mentorship as an overlooked dimension of research capacity strengthening: how to embed value-driven practices in global health., BMJ Glob Health, Vol: 9, ISSN: 2059-7908

Mentorship in global health remains an overlooked dimension of research partnerships. Commitment to effective mentorship models requires value-driven approaches. This includes having an understanding of (1) what mentorship means across different cultural and hierarchical boundaries in the health research environment, and (2) addressing entrenched power asymmetries across different aspects including funding, leadership, data and outputs, and capacity strengthening. Existing guidance towards equity and sustainability fails to inform how to navigate complex relationships which hinder effective mentorship models. We focus this perspective piece on human capacity strengthening in research partnerships through mentorship. Using a case study of a research partnership, we describe the lessons learnt and the challenges faced in the mentor mentee relationship while maintaining an effective and sustainable partnership. Human capacity strengthening must research projects and collaborations, and recognise local leadership and ownership. To be transformative and effective, practices need to be driven by common values across research teams.

Journal article

Birgand G, Biccard B, Deslandes A, Mbamalu O, Bonaconsa C, Boutall A, Mendelson M, Leone M, Ndoli J, Leather A, Holmes A, Moonesinghe R, Charani Eet al., 2024, Role of anaesthesia providers in infection-related care across the perioperative pathway: a global survey., Br J Anaesth, Vol: 132, Pages: 197-200

Journal article

Mbamalu O, Bonaconsa C, Surendran S, Nampoothiri V, Pennel T, Boutall A, Papavarnavas N, Singh S, Holmes A, Charani E, Mendelson Met al., 2023, Missed opportunities for hand hygiene at the patient's bedside: a pilot descriptive study., J Hosp Infect

Journal article

Birgand G, Dhar P, Holmes A, 2023, The threat of antimicrobial resistance in surgical care: the surgeon’s role and ownership of antimicrobial stewardship, British Journal of Surgery, Vol: 110, Pages: 1567-1569, ISSN: 0007-1323

Journal article

Miglietta L, Chen Y, Luo Z, Xu K, Ding N, Peng T, Moniri A, Kreitmann L, Cacho-Soblechero M, Holmes A, Georgiou P, Rodriguez-Manzano Jet al., 2023, Smart-Plexer: a breakthrough workflow for hybrid development of multiplex PCR assays., Communications Biology, Vol: 6, ISSN: 2399-3642

Developing multiplex PCR assays requires extensive experimental testing, the number of which exponentially increases by the number of multiplexed targets. Dedicated efforts must be devoted to the design of optimal multiplex assays ensuring specific and sensitive identification of multiple analytes in a single well reaction. Inspired by data-driven approaches, we reinvent the process of developing and designing multiplex assays using a hybrid, simple workflow, named Smart-Plexer, which couples empirical testing of singleplex assays and computer simulation to develop optimised multiplex combinations. The Smart-Plexer analyses kinetic inter-target distances between amplification curves to generate optimal multiplex PCR primer sets for accurate multi-pathogen identification. In this study, the Smart-Plexer method is applied and evaluated for seven respiratory infection target detection using an optimised multiplexed PCR assay. Single-channel multiplex assays, together with the recently published data-driven methodology, Amplification Curve Analysis (ACA), were demonstrated to be capable of classifying the presence of desired targets in a single test for seven common respiratory infection pathogens.

Journal article

Panca M, Blackstone J, Stirrup O, Cutino-Moguel M-T, Thomson E, Peters C, Snell LB, Nebbia G, Holmes A, Chawla A, Machin N, Taha Y, Mahungu T, Saluja T, de Silva TI, Saeed K, Pope C, Shin GY, Williams R, Darby A, Smith DL, Loose M, Robson SC, Laing K, Partridge DG, Price JR, Breuer Jet al., 2023, Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals, JOURNAL OF HOSPITAL INFECTION, Vol: 139, Pages: 23-32, ISSN: 0195-6701

Journal article

Campbell A, Borek AJ, McLeod M, Tonkin-Crine S, Pouwels KB, Roope LS, Hayhoe BW, Majeed A, Walker AS, Holmes A, STEP-UP teamet al., 2023, Impact of the COVID-19 pandemic on antimicrobial stewardship support for general practices in England: a qualitative interview study., BJGP Open, Vol: 7

BACKGROUND: In England, clinical commissioning group (CCG; now replaced by Integrated Care Systems [ICSs]) and primary care network (PCN) professionals support primary care prescribers to optimise antimicrobial stewardship (AMS). AIM: To explore views and experiences of CCG and PCN staff in supporting AMS, and the impact of COVID-19 on this support. DESIGN & SETTING: Qualitative interview study in primary care in England. METHOD: Semi-structured interviews with staff from CCG and PCNs responsible for AMS were conducted at two timepoints via telephone. These were audio-recorded, transcribed, and analysed thematically. RESULTS: Twenty-seven interviews were conducted with 14 participants (nine CCG, five PCN) in December 2020-January 2021 and February-May 2021. The study found that AMS support was (1) deprioritised in order to keep general practice operational and deliver COVID-19 vaccines; (2) disrupted as social distancing made it harder to build relationships, conduct routine AMS activities, and challenge prescribing decisions; and (3) adapted, with opportunities identified for greater use of technology and changing patient and public perceptions of viruses and self-care. It was also found that resources to support AMS were valued if they were both novel, to counter AMS 'fatigue', and sufficiently familiar to fit with existing and/or future AMS. CONCLUSION: AMS needs to be reprioritised in general practice in the post-pandemic era and within the new ICSs in England. This should include interventions and strategies that combine novel elements with already familiar strategies to refresh prescribers' motivation and opportunities for AMS. Behaviour change interventions should be aimed at improving the culture and processes for how PCN pharmacists voice concerns about AMS to prescribers in general practice and take advantage of the changed patient and public perceptions of viruses and self-care.

Journal article

Chanh HQ, Ming DK, Nguyen QH, Duc TM, An LP, Trieu HT, Karolcik S, Hernandez B, Perez J, Van Nuil J, Lyle NN, Kestelyn E, Thwaites L, Georgiou P, Paton C, Holmes A, Chau NVV, Yacoub Set al., 2023, Applying artificial intelligence and digital health technologies, Viet Nam, BULLETIN OF THE WORLD HEALTH ORGANIZATION, Vol: 101, Pages: 487-492, ISSN: 0042-9686

Journal article

Myall A, Venkatachalam I, Philip C, Yin M, Koon D, Arora S, Yue Y, Peach R, Weisse A, Tambyah P, Chow A, Price J, Cook A, Holmes A, Barahona Met al., 2023, SPATIAL-TEMPORAL DETERMINANTS OF MDRO TRANSMISSION DYNAMICS: IMPLICATIONS FOR INFECTION CONTROL, Publisher: ELSEVIER SCI LTD, Pages: S31-S31, ISSN: 1201-9712

Conference paper

Myall A, Wiedermann M, Vasikasin P, Klamser P, Wan Y, Zachariae A, Peach R, Dorigatti I, Kreitmann L, Rodgus J, Getino-Redondo M, Mookerje S, Jauneikaite E, Davies F, Weisse A, Price J, Holmes A, Barahona M, Brockmann Det al., 2023, RECONSTRUCTING AND PREDICTING THE SPATIAL EVOLUTION OF CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE OUTBREAKS, Publisher: ELSEVIER SCI LTD, Pages: S65-S65, ISSN: 1201-9712

Conference paper

Nampoothiri V, Mbamalu O, Surendran S, Bonaconsa C, Pennel T, Boutall A, Gopal K, Sanchez EC, Dhar P, Holmes A, Singh S, Mendelson M, Tarrant C, Charani E, ASPIRES CIet al., 2023, The elephant in the room: Exploring the influence and participation of patients in infection-related care across surgical pathways in South Africa and India, HEALTH EXPECTATIONS, Vol: 26, Pages: 892-904, ISSN: 1369-6513

Journal article

Vasikasin V, Rawson TM, Holmes AH, Otter Jet al., 2023, Can precision antibiotic prescribing help prevent the spread of carbapenem-resistant organisms in the hospital setting?, JAC-Antimicrobial Resistance, Vol: 5, Pages: 1-13, ISSN: 2632-1823

The emergence of carbapenem-resistant organisms (CROs) is a significant global threat. Reduction of carbapenem consumption can decrease CROs. In the global endemic era of ESBL-producing bacteria, carbapenems are considered the treatment of choice, leading to challenge in limiting carbapenem use. This review describes the role of precision prescribing for prevention of CROs. This involves improving antibiotic selection, dosing and shortening duration. The effect of different antibiotics, dosing and duration on CRO development are explored. Available options for precision prescribing, gaps in the scientific evidence, and areas for future research are also presented.

Journal article

Karolcik S, Ming D, Yacoub S, Holmes A, Georgiou Pet al., 2023, A multi-site, multi-wavelength PPG platform for continuous non-invasive health monitoring in hospital settings, IEEE Transactions on Biomedical Circuits and Systems, Vol: 17, Pages: 349-361, ISSN: 1932-4545

This paper presents a novel PPG acquisition platform capable of synchronous multi-wavelength signal acquisition from two measurement locations with up to 4 independent wavelengths from each in parallel. The platform is fully configurable and operates at 1ksps, accommodating a wide variety of transmitters and detectors to serve as both a research tool for experimentation and a clinical tool for disease monitoring. The sensing probes presented in this work acquire 4 PPG channels from the wrist and 4 PPG channels from the fingertip, with wavelengths such that surrogates for pulse wave velocity and haematocrit can be extracted.For conventional PPG sensing, we have achieved the mean error of 4.08 ± 3.72 bpm for heart-rate and a mean error of 1.54 ± 1.04% for SpO2 measurement, with the latter lying within the FDA limits for commercial pulse oximeters. We have further evaluated over 700 individual peak-to-peak time differences between wrist and fingertip signals, achieving a normalized weighted average PWV of 5.80 ± 1.58 m/s, matching with values of PWV found for this age group in literature. Lastly, we introduced and computed a haematocrit ratio (Rhct) between the deep IR and deep red wavelength from the fingertip sensor, finding a significant difference between male and female values (median of 1.9 and 2.93 respectively) pointing to devices sensitivity to Hct.

Journal article

Freeman DME, Ming DK, Wilson R, Herzog PL, Schulz C, Felice AKG, Chen Y-C, O'Hare D, Holmes AH, Cass AEGet al., 2023, Continuous Measurement of Lactate Concentration in Human Subjects through Direct Electron Transfer from Enzymes to Microneedle Electrodes, ACS SENSORS, ISSN: 2379-3694

Journal article

Mao Y, Miglietta L, Kreitmann L, Moser N, Georgiou P, Holmes A, Rodriguez Manzano Jet al., 2023, Deep domain adaptation enhances Amplification Curve Analysis for single-channel multiplexing in real-time PCR, IEEE Journal of Biomedical and Health Informatics, Vol: 27, Pages: 3093-3103, ISSN: 2168-2208

Data-driven approaches for molecular diagnostics are emerging as an alternative to perform an accurate and inexpensive multi-pathogen detection. A novel technique called Amplification Curve Analysis (ACA) has been recently developed by coupling machine learning and real-time Polymerase Chain Reaction (qPCR) to enable the simultaneous detection of multiple targets in a single reaction well. However, target classification purely relying on the amplification curve shapes currently faces several challenges, such as distribution discrepancies between different data sources of synthetic DNA and clinical samples (i.e., training vs testing). Optimisation of computational models is required to achieve higher performance of ACA classification in multiplex qPCR through the reduction of those discrepancies. Here, we proposed a novel transformer-based conditional domain adversarial network (T-CDAN) to eliminate data distribution differences between the source domain (synthetic DNA data) and the target domain (clinical isolate data). The labelled training data from the source domain and unlabelled testing data from the target domain are fed into the T-CDAN, which learns both domains' information simultaneously. After mapping the inputs into a domain-irrelevant space, T-CDAN removes the feature distribution differences and provides a clearer decision boundary for the classifier, resulting in a more accurate pathogen identification. Evaluation of 198 clinical isolates containing three types of carbapenem-resistant genes ( bla NDM , bla IMP and bla OXA-48 ) illustrates a curve-level accuracy of 93.1% and a sample-level accuracy of 97.0% using T-CDAN, showing an accuracy improvement of 20.9% and 4.9% respectively, compared with previous methods. This research emphasises the importance of deep domain adaptation to enable high-level multiplexing in a single qPCR reaction, providing a solid approach to extend qPCR instruments' capabilities without hardware modification in real-world cli

Journal article

Kreitmann L, Miglietta L, Xu K, Malpartida-Cardenas K, D'Souza G, Kaforou M, Brengel-Pesce K, Drazek L, Holmes A, Rodriguez-Manzano Jet al., 2023, Next-generation molecular diagnostics: Leveraging digital technologies to enhance multiplexing in real-time PCR, TrAC Trends in Analytical Chemistry, Vol: 160, Pages: 1-11, ISSN: 0165-9936

Real-time polymerase chain reaction (qPCR) enables accurate detection and quantification of nucleic acids and has become a fundamental tool in biological sciences, bioengineering and medicine. By combining multiple primer sets in one reaction, it is possible to detect several DNA or RNA targets simultaneously, a process called multiplex PCR (mPCR) which is key to attaining optimal throughput, cost-effectiveness and efficiency in molecular diagnostics, particularly in infectious diseases. Multiple solutions have been devised to increase multiplexing in qPCR, including single-well techniques, using target-specific fluorescent oligonucleotide probes, and spatial multiplexing, where segregation of the sample enables parallel amplification of multiple targets. However, these solutions are mostly limited to three or four targets, or highly sophisticated and expensive instrumentation. There is a need for innovations that will push forward the multiplexing field in qPCR, enabling for a next generation of diagnostic tools which could accommodate high throughput in an affordable manner.To this end, the use of machine learning (ML) algorithms (data-driven solutions) has recently emerged to leverage information contained in amplification and melting curves (AC and MC, respectively) – two of the most standard bio-signals emitted during qPCR – for accurate classification of multiple nucleic acid targets in a single reaction. Therefore, this review aims to demonstrate and illustrate that data-driven solutions can be successfully coupled with state-of-the-art and common qPCR platforms using a variety of amplification chemistries to enhance multiplexing in qPCR.Further, because both ACs and MCs can be predicted from sequence data using thermodynamic databases, it has also become possible to use computer simulation to rationalize and optimize the design of mPCR assays where target detection is supported by data-driven technologies. Thus, this review also discusses recent

Journal article

Charani ESMITA, Mendelson M, Pallett S, Ahmad R, Mpundu M, Mbamalu O, Bonaconsa C, Nampoothiri V, Singh S, Peiffer-Smadja N, Anton-Vazquez V, Moore L, Schouten J, Kostyanev T, Vlahovic-Palcevski V, Kofteridis D, Correa J, Holmes Aet al., 2023, An analysis of existing National Action Plans for antimicrobial resistance – gaps and opportunities in strategies optimising antibiotic use in human populations, The Lancet Global Health, Vol: 11, Pages: e466-e474, ISSN: 2214-109X

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.

Journal article

Mbamalu O, Surendran S, Nampoothiri V, Bonaconsa C, Edathadathil F, Zhu N, Lambert H, Tarrant C, Ahmad R, Boutall A, Brink A, Steenkamp E, Holmes A, Singh S, Charani E, Mendelson Met al., 2023, Survey of healthcare worker perceptions of changes in infection control and antimicrobial stewardship practices in India and South Africa during the COVID-19 pandemic., IJID Reg, Vol: 6, Pages: 90-98

OBJECTIVE: To identify perceptions and awareness of changes in infection prevention and control (IPC) and antimicrobial stewardship (AMS) practices among healthcare workers (HCWs) during the COVID-19 pandemic in India and South Africa (SA). METHOD: A self-administered online survey which included participant demographics, knowledge and sources of COVID-19 infection, perceived risks and barriers, and self-efficacy. Data were analysed using descriptive statistics. RESULTS: The study received 321 responses (response rate: 89.2%); 131/321 (40.8%) from India and 190/321 (59.2%) from SA; male to female response rate was 3:2, with majority of respondents aged 40-49 (89/321, 27.7%) and 30-39 (87/321, 27.1%) years. Doctors comprised 47.9% (57/119) of respondents in India and 74.6% (135/181) in SA. Majority of respondents in India (93/119, 78.2%) and SA (132/181, 72.9%) were from the private and public sectors, respectively, with more respondents in SA (123/174, 70.7%) than in India (38/104, 36.5%) involved in antimicrobial prescribing.Respondents reported increased IPC practices since the pandemic and noted a need for more training on case management, antibiotic and personal protective equipment (PPE) use. While they noted increased antibiotic prescribing since the pandemic, they did not generally associate their practice with such an increase. A willingness to be vaccinated, when vaccination becomes available, was expressed by 203/258 (78.7%) respondents. CONCLUSIONS: HCWs reported improved IPC practices and changes in antibiotic prescribing during the COVID-19 pandemic. Targeted education on correct use of PPE was an identified gap. Although HCWs expressed concerns about antimicrobial resistance, their self-perceived antibiotic prescribing practices seemed unchanged. Additional studies in other settings could explore how our findings fit other contexts.

Journal article

Hernandez Perez B, Stiff O, Ming D, Ho Quang C, Vuong Nguyen L, Tuan Nguyen M, Chau Nguyen VV, Nguyet Nguyen M, Huy Nguyen Q, Lam Phung K, Tam Dong Thi H, Trung Dinh T, Trieu Huynh T, Wills B, Cameron Paul S, Holmes A, Yacoub S, Georgiou Pet al., 2023, Learning meaningful latent space representations for patient risk stratification: model development and validation for dengue and other acute febrile illness, Frontiers in Digital Health, Vol: 5, Pages: 1-16, ISSN: 2673-253X

Background: Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented.Methods: We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications.Results: The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman

Journal article

Riezk A, Vasikasin V, Wilson RCC, Rawson TMM, McLeod JGG, Dhillon R, Duckers J, Cass AEG, Holmes AHHet al., 2023, Triple quadrupole LC/MS method for the simultaneous quantitative measurement of cefiderocol and meropenem in serum, Analytical Methods: advancing methods and applications, Vol: 15, Pages: 746-751, ISSN: 1759-9660

Background: therapeutic drug monitoring is a crucial aspect of the management of hospitalized patients. The correct dosage of antibiotics is imperative to ensure their adequate exposure specially in critically ill patients. The aim of this study is to establish and validate a robust and fast liquid chromatography-tandem mass spectrometry (LC/MS) method for the simultaneous quantification of two important antibiotics in critically ill patients, cefiderocol and meropenem in human plasma. Methods: sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using triple quadrupole LC/MS. The mobile phase was consisted of 55% methanol in water +0.1% formic acid, with flow rate of 0.4 ml min−1. Antibiotics stability was assessed at different temperatures. Serum protein binding was assessed using ultrafiltration devices. Results: chromatographic separation was achieved within 1.5 minutes for all analytes. Validation has demonstrated the method to be linear over the range 0.0025–50 mg L−1 for cefiderocol and 0.00028–50 mg L−1 for meropenem, with accuracy of 94–101% and highly sensitive, with LLOQ ≈ 0.02 mg L−1 and 0.003 mg L−1 for cefiderocol and meropenem, respectively. Both cefiderocol and meropenem showed a good stability at room temperature over 6 h, and at (4 °C) over 24 h. Cefiderocol and meropenem demonstrated a protein binding of 49–60% and 98%, respectively in human plasma. Conclusion: the developed method is simple, rapid, accurate and clinically applicable for the quantification of cefiderocol and meropenem.

Journal article

Riezk A, Wilson RC, Rawson TM, Vasikasin V, Arkel P, Ferris TJ, Haigh LD, Cass AEG, Holmes AHet al., 2023, A rapid, simple, high-performance liquid chromatography method for the clinical measurement of beta-lactam antibiotics in serum and interstitial fluid, Analytical Methods: advancing methods and applications, Vol: 15, Pages: 829-836, ISSN: 1759-9660

Background: enhanced methods of therapeutic drug monitoring are required to support the individualisation of antibiotic dosing based on pharmacokinetics (PK) parameters. PK studies can be hampered by limited total serum volume, especially in neonates, or by sensitivity in the case of critically ill patients. We aimed to develop a liquid chromatography–mass spectrometry (LC/MS) analysis of benzylpenicillin, phenoxymethylpenicillin and amoxicillin in single low volumes of human serum and interstitial fluid (ISF) samples, with an improved limit of detection (LOD) and limit of quantification (LOQ), compared with previously published assays. Methods: sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using triple quadrupole LC/MS. The mobile phase consisted of 55% methanol in water + 0.1% formic acid, with a flow rate of 0.4 mL min−1. Antibiotics stability was assessed at different temperatures. Results: chromatographic separation was achieved within 3 minutes for all analytes. Three common penicillins can now be measured in a single low-volume blood and ISF sample (15 μL) for the first time. Validation has demonstrated the method to be linear over the range 0.0015–10 mg L−1, with an accuracy of 93–104% and high sensitivity, with LOD ≈ 0.003 mg L−1 and LOQ ≈ 0.01 mg L−1 for all three analytes, which is critical for use in dose optimisation/individualisation. All evaluated penicillins indicated good stability at room temperature over 4 h, at (4 °C) over 24 h and at −80 °C for 6 months. Conclusion: the developed method is simple, rapid, accurate and clinically applicable for the quantification of three penicillin classes.

Journal article

Ming D, Nguyen QH, An LP, Chanh HQ, Tam DTH, Truong NT, Huy VX, Hernandez B, Van Nuil JI, Paton C, Georgiou P, Nguyen NM, Holmes A, Tho PV, Yacoub Set al., 2023, Mapping patient pathways and understanding clinical decision-making in dengue management to inform the development of digital health tools, BMC Medical Informatics and Decision Making, Vol: 23, Pages: 1-9, ISSN: 1472-6947

BackgroundDengue is a common viral illness and severe disease results in life-threatening complications. Healthcare services in low- and middle-income countries treat the majority of dengue cases worldwide. However, the clinical decision-making processes which result in effective treatment are poorly characterised within this setting. In order to improve clinical care through interventions relating to digital clinical decision-support systems (CDSS), we set out to establish a framework for clinical decision-making in dengue management to inform implementation.MethodsWe utilised process mapping and task analysis methods to characterise existing dengue management at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. This is a tertiary referral hospital which manages approximately 30,000 patients with dengue each year, accepting referrals from Ho Chi Minh city and the surrounding catchment area. Initial findings were expanded through semi-structured interviews with clinicians in order to understand clinical reasoning and cognitive factors in detail. A grounded theory was used for coding and emergent themes were developed through iterative discussions with clinician-researchers.ResultsKey clinical decision-making points were identified: (i) at the initial patient evaluation for dengue diagnosis to decide on hospital admission and the provision of fluid/blood product therapy, (ii) in those patients who develop severe disease or other complications, (iii) at the point of recurrent shock in balancing the need for fluid therapy with complications of volume overload. From interviews the following themes were identified: prioritising clinical diagnosis and evaluation over existing diagnostics, the role of dengue guidelines published by the Ministry of Health, the impact of seasonality and caseload on decision-making strategies, and the potential role of digital decision-support and disease scoring tools.ConclusionsThe study highlights the contemporary priorities i

Journal article

Otter JA, Zhou J, Price JR, Reeves L, Zhu N, Randell P, Sriskandan S, Barclay WS, Holmes AHet al., 2023, SARS-CoV-2 surface and air contamination in an acute healthcare setting during the first and second pandemic waves, JOURNAL OF HOSPITAL INFECTION, Vol: 132, Pages: 36-45, ISSN: 0195-6701

Journal article

Mbamalu O, Surendran S, Nampoothiri V, Bonaconsa C, Edathadathil F, Zhu N, Carter V, Lambert H, Tarrant C, Ahmad R, Brink A, Steenkamp E, Holmes A, Singh S, Charani E, Mendelson Met al., 2023, A survey of patient and public perceptions and awareness of SARS-CoV-2-related risks among participants in India and South Africa., PLOS Glob Public Health, Vol: 3

A cross-sectional survey among participants in India and South Africa to explore perceptions and awareness of SARS-CoV-2-related risks. Main outcome measures-proportion of participants aware of SARS-CoV-2, and their perception of infection risks as it related to their views and perceptions on vaccination, i.e., using COVID-19 vaccine uptake as proxy for awareness level. Self-administered questionnaires were used to collect data via web- and paper-based surveys over three months. Pearson's Chi-squared test assessed relationships between variables; a p-value less than 0.05 was considered significant. There were 844 respondents (India: n = 660, South Africa: n = 184; response rate 87.6%), with a 61.1% vs 38.3% female to male ratio. Post-high-school or university education was the lowest qualification reported by most respondents in India (77.3%) and South Africa (79.3%). Sources of pandemic information were usually media and journal publications (73.2%), social media (64.6%), family and friends (47.7%) and government websites (46.2%). Most respondents correctly identified infection prevention measures (such as physical distancing, mask use), with 90.0% reporting improved hand hygiene practices since the pandemic. Hesitancy or refusal to accept the SARS-CoV-2 vaccine was reported among 17.9% and 50.9% of respondents in India and South Africa, respectively; reasons cited included rushed vaccine development and the futility of vaccines for what respondents considered a self-limiting flu-like illness. In South Africa, vaccine acceptance was associated with improved hand hygiene practices since the pandemic and flu vaccination in the preceding year. No relationship was noted between awareness and practice of infection prevention measures (such as hand hygiene) and socio-demographic factors such as employment status or availability of amenities. Pandemic response and infection prevention and control measures through vaccination campaigns should consider robust public engagem

Journal article

Arkell P, Mairiang D, Songjaeng A, Malpartida-Cardenas K, Hill-Cawthorne K, Avirutnan P, Georgiou P, Holmes A, Rodriguez-Manzano Jet al., 2023, Analytical and diagnostic performance characteristics of reverse-transcriptase loop-mediated isothermal amplification assays for dengue virus serotypes 1-4: A scoping review to inform potential use in portable molecular diagnostic devices., PLOS Glob Public Health, Vol: 3

Dengue is a mosquito-borne disease caused by dengue virus (DENV) serotypes 1-4 which affects 100-400 million adults and children each year. Reverse-transcriptase (RT) quantitative polymerase chain reaction (qPCR) assays are the current gold-standard in diagnosis and serotyping of infections, but their use in low-middle income countries (LMICs) has been limited by laboratory infrastructure requirements. Loop-mediated isothermal amplification (LAMP) assays do not require thermocycling equipment and therefore could potentially be deployed outside laboratories and/or miniaturised. This scoping literature review aimed to describe the analytical and diagnostic performance characteristics of previously developed serotype-specific dengue RT-LAMP assays and evaluate potential for use in portable molecular diagnostic devices. A literature search in Medline was conducted. Studies were included if they were listed before 4th May 2022 (no prior time limit set) and described the development of any serotype-specific DENV RT-LAMP assay ('original assays') or described the further evaluation, adaption or implementation of these assays. Technical features, analytical and diagnostic performance characteristics were collected for each assay. Eight original assays were identified. These were heterogenous in design and reporting. Assays' lower limit of detection (LLOD) and linear range of quantification were comparable to RT-qPCR (with lowest reported values 2.2x101 and 1.98x102 copies/ml, respectively, for studies which quantified target RNA copies) and analytical specificity was high. When evaluated, diagnostic performance was also high, though reference diagnostic criteria varied widely, prohibiting comparison between assays. Fourteen studies using previously described assays were identified, including those where reagents were lyophilised or 'printed' into microfluidic channels and where several novel detection methods were used. Serotype-specific DENV RT-LAMP assays are high-perform

Journal article

Birgand G, Ahmad R, Bulabula ANH, Singh S, Bearman G, Sanchez EC, Holmes Aet al., 2022, Innovation for infection prevention and control-revisiting Pasteur's vision, LANCET, Vol: 400, Pages: 2250-2260, ISSN: 0140-6736

Journal article

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