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Impact of molecular point-of-care testing for respiratory pathogens on antibiotic use and clinical outcomes in acute respiratory tract infections: a systematic review and meta-analysis
No full textBackground: Molecular point-of-care testing (mPOCT) offers rapid identification of respiratory pathogens, but its impact on antibiotic use and patient outcomes remains uncertain. We aimed to comprehensively evaluate the effects of mPOCT on antibiotic use and major clinical outcomes in patients presenting with acute respiratory tract infections (ARTIs). Methods: We searched MEDLINE, Embase, Web of Science, CENTRAL, CNKI, and Wanfang Data from inception to July 1, 2025, for randomised controlled trials (RCTs) evaluating mPOCT for patients presenting with ARTIs (PROSPERO CRD420251069333). The primary outcome was antibiotic use, assessed using pooled risk ratio (RR) with random-effects models. Risk of bias and certainty of evidence were assessed using the Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials (ROBUST-RCT) and core Grading of Recommendations, Assessment, Development and Evaluation (GRADE), respectively. Findings: We included 25 RCTs involving 12,638 patients, of whom 61.0% were adults. Overall, mPOCT probably had little to no important effect on antibiotic use (RR 0.95, 95% CI 0.90–1.00; moderate certainty) or treatment duration (mean difference −0.44 days, 95% CI −0.98 to 0.09; moderate certainty). In adults, high-certainty evidence showed no effect on antibiotic use (RR 1.00, 95% CI 0.98–1.02), whereas in children, low-certainty evidence suggested a potential reduction (RR 0.79, 95% CI 0.65–0.97). Although mPOCT increased appropriate antibiotic prescribing (RR 2.07, 95% CI 1.55–2.77; moderate certainty), it did not affect 30-day mortality (RR 0.97, 95% CI 0.82–1.15; high certainty) and intensive care unit admission (RR 0.90, 95% CI 0.65–1.25; high certainty). Interpretation: Moderate to high certainty evidence suggests that mPOCT does not meaningfully reduce overall antibiotic use or improve patient outcomes, particularly in adults, despite enhancing prescribing appropriateness. Routine use of mPOCT for adults with ARTIs is therefore not supported
30-day readmission risk after hip fracture: a qualitative study in the Midlands, United Kingdom
No full textBackground: Reducing unplanned 30-day readmission is imperative across health systems; particularly if they result from clinical failings, avoidable harms and are associated with unnecessary expenditure. This study aimed to identify interventions capable of reducing avoidable 30-day readmission after fragility fracture of the hip in an area of high socio-economic deprivation in the United Kingdom (UK) and understand how these interventions could be informed by behaviour change theory. Methods: A qualitative study was undertaken in the Midlands region of the UK in the National Health Service. Observational fieldwork of healthcare staff meetings, interviews with patients following hip fracture, carers and staff, and a theoretical mapping exercise were undertaken to examine patient’s journeys and factors affecting service delivery that might impact readmission risk. Observations were documented using electronic field notes. Semi-structured interviews explored experiences of the admission/readmission, transitions in care, readmission risks and interventions capable of reducing avoidable readmission. Analysis was conducted in four parts: 1) Inductive thematic analysis of interview and observational data explored patient journeys 2) Dyadic interviews analysis examined agreement/divergence within accounts 3) Deductive analysis identified readmission risk factors and candidate interventions 4) Candidate interventions were mapped with the constructs of the Theoretical Domains Framework. UK REC and HRA approval was obtained 3/WM/0242. Results: Eleven non-participant observations were conducted in healthcare staff meetings in community (3) and acute (8) settings. Twenty-Four interviews were completed with 11 staff (five occupational therapists, three physiotherapists, one doctor, one trainee nurse practitioner, and one physiotherapy assistant), eight patients and five of the patients’ carers during July-September 2024. Three high level themes were identified – perceived burden, communication challenges and the health and social care system. Twenty-two candidate interventions relating to four challenges were identified: 1) adequacy of information, 2) individualised care, 3) access to services and 4) the hip fracture pathway. Conclusions: This study identified interventions which staff, patients and carers proposed might reduce avoidable readmission after hip fracture in an area of high deprivation. Further work is needed to refine and rank the proposed interventions followed by an implementation plan to explain mode of delivery and who needs to do what differently
An assessment of the ecosystem services content of green plans as an evaluation proxy for the delivery of urban green infrastructure
No full textTo facilitate well-being and health amongst urban populations, there is a need for urban spatial plans to promote sustainable development, leading to considerable interest and practice related to the delivery of urban green infrastructure (UGI). One approach for delivering UGI is through the adoption of green plans. However, green plans vary considerably in their structure and content, and there is a pressing need to evaluate whether green plans incorporate the necessary range of ecosystem services (ES). In this paper, we adopt an existing evaluation method using coding to determine the extent to which ES are embedded explicitly and implicitly in green plans. We apply this to a unique situation of the Brazilian city of São Paulo which has four separate green plans (investigating each plan individually for potential ES delivery) and adapt the method to separate the rhetoric of plans from their tangible actions in order to get closer to an analysis of ES outcomes. The four green plans that make up the green area system present greater or lesser participation and intensity of the ES concept which can influence the UGI implementation. However, the analysis comparing the content and discursive representation of each green plan with its respective plan actions showed, except for one of the four plans, that the delivery of ES through the green plans focuses more on rhetoric than action. To deliver the desired UGI for ensuring urban sustainability, green plans must not only mention ES in their content but should embed ES in their plan actions
Evaluation of the CompreHensive geriAtRician-led MEdication Review (CHARMER) Deprescribing Intervention in Hospital: Protocol for a Cluster Randomised Stepped-Wedge Trial
Get PDFBackground: Whilst almost half of older adults admitted to hospital are prescribed potentially inappropriate medicines, less than 1% have a medicine proactively deprescribed during admission in the UK. The CompreHensive geriAtRician-led MEdication Review (CHARMER) intervention, is designed to address geriatricians’ and pharmacists’ barriers and enablers to deprescribing. The CHARMER definitive trial will evaluate effectiveness, cost-effectiveness and safety. Methods and analysis: A stepped-wedge cluster randomised controlled trial will be conducted in 20 hospitals in England, with four hospitals in reserve. All hospitals will collect baseline data. Every three months, five hospitals will be randomised to receive the intervention. The intervention, implemented by a local project manager, comprises: A hospital action plan to set deprescribing as an organisational goal; workshops for pharmacists and geriatricians to change beliefs about deprescribing; weekly briefings between geriatricians and pharmacists to discuss opportunities for deprescribing; benchmarking reports to compare deprescribing performance across participating hospitals. With an average 200 patients admitted and discharged during each step, the study will have 89.5% power at 5% significance level and ICC of 0.05 to detect a 3% difference in 90-day re-admission rate from 16.7% versus 13.7%. Anonymised routinely collected data, including readmissions will be obtained for all patients admitted during the study period. Enhanced data collection periods of one month during control and intervention periods will be used to recruit patients and data for secondary outcomes and process evaluation. Ethics and dissemination: Ethical approval for the study was obtained from Wales REC2 on 04/07/2023, REF: 23/WA/0184. Confidential Advisory Group approval (REF: 23/CAG/0073) was obtained on 06/07/2023 to enable collection of anonymised routinely collected data for all participants during the non-enhanced data collection periods. The research team will follow the Guide to Disseminating Research (GuiDir) framework, which includes identification of target audiences for dissemination from the outset, agreeing dissemination goals, developing a dissemination plan, choosing appropriate dissemination channels and tracking the impact of the dissemination. Depending on the trial result the goal would ultimately be national implementation of intervention and consequently target audiences will include service commissioners and representative bodies for the different actors within the trial
Dioxygen Activation by Caenorhabditis elegans Ferritin: The Effect of the Second Coordination Sphere on O2 reduction to H2O2
Get PDFFerritins are important proteins that store and detoxify iron. They contain a diiron active site that can convert dioxygen into hydrogen peroxide. The active site contains many hydrogen bonding interactions and charged residues and hence the precise mechanism is not well defined. In this work a comprehensive computational study using molecular dynamics and quantum mechanics is presented on the structure and reactivity of dioxygen binding at the diiron(II) active site of a ferritin from the worm Caenorhabditis elegans. The molecular dynamics simulation gives a rigid protein structure due to the large number of polar interactions between residues and solvent water molecules. The calculated dioxygen activation is stepwise with two successive proton transfer steps via an iron(III)-hydroperoxo intermediate. The calculations provide novel insight into the role of the strictly conserved near-active site Tyr residue, which appears to be important for hydrogen bonding and positioning of dioxygen into the active site
Determining the dissociation and binding dynamics of molecules using 1H NMR chemical shift imaging techniques
Get PDFThis PhD thesis introduces and applies new methodologies based on Nuclear Magnetic Resonance (NMR) chemical shift imaging (CSI) to measure acid dissociation constants (pKa) and metal–ligand binding dynamics in situ. The research addresses longstanding challenges in characterizing systems that are difficult to analyse by conventional means (such as polymers with broad NMR signals or systems requiring numerous titrations) by leveraging controlled chemical gradients within a single NMR tube. In one approach, a derivative-based fitting method was developed to determine pKa from 1H NMR titration data. By analysing the derivative of solution pH with respect to the observed chemical shift (δobs) of an analyte, this method circumvents the need to fit limiting chemical shift values and avoids convergence issues associated with traditional nonlinear regression. It enables rapid, robust pKa determination via a simple polynomial fit, yielding values in excellent agreement with literature standards while reducing the data requirements and time cost of titrations.
The subsequent chapter expands NMR pKa measurements to NMR-invisible species (e.g. macromolecules or ions whose proton signals are unobservable or too broad) by coupling CSI with indicators that measure the quantity of protons transferred to them from the analyte. Using a controlled pH gradient in a single “one-shot” CSI experiment, the quantity of protons transferred from an “invisible” analyte to an NMR-visible indicator is measured across space, enabling calculation of the analyte’s pKa and concentration without direct observation of its own signals. This technique was validated on model systems including a high-molecular-weight polymer (polyacrylic acid) and a protein (wheat germ agglutinin), successfully yielding pKa values consistent with their known behaviour. The method proved effective even when analyte NMR peaks were severely broadened or overlapping, demonstrating its versatility for complex mixtures. Furthermore, the thesis extends CSI-based titration to heterogeneous solvent systems: by establishing a solvent (water-Dimethyl sulfoxide) gradient, spatially resolved pH measurements were used to determine solvent dependent pKa values (psKa) of organic compounds across different solvent compositions. These data were extrapolated (via the Yasuda Shedlovsky method) to estimate the true aqueous pKa, providing a novel route to obtain dissociation constants of sparingly water-soluble molecules.
Finally, a single-tube CSI method for metal ligand binding is presented. Here, a concentrated salt (calcium or magnesium acetate) is layered beneath an aqueous solution of a ligand (such as a polymer or small organic acid), generating an upward diffusion gradient of metal ions.1H CSI is then used to map spatial profiles of free metal concentration [M2+]f (monitored via weak binding indicator molecules whose chemical shifts report on M2+ binding) and the total diffusant (acetate) concentration. From the mismatch between the acetate profile and the free M2+ profile, the local amount of metal bound to the ligand (B) is quantified. This approach was tested on strong, multivalent binders like oxalate or alginate which showed pronounced metal uptake, essentially sequestering Ca2+ and Mg2+ until saturation of their binding sites. In contrast, weak binders such as carboxymethyl cellulose (CMC) and gallic acid exhibited negligible binding, yielding free ion profiles almost overlapping with the control (no ligand) case. These findings quantitatively confirm expectations (e.g. alginate’s well-known Ca2+ crosslinking behaviour and CMC’s minimal interaction with divalent cations) and provide new insights such as the precise point of Ca2+ induced cellulose nanocrystal aggregation.
Overall, the thesis demonstrates that CSI can be harnessed to obtain detailed thermodynamic parameters such pKa values and complexation capacities directly within an NMR tube. The developed techniques require only standard high-field NMR hardware and small sample quantities, yet achieve spatially resolved, multi point measurements in a single run. The outcomes not only corroborate traditional measurements but also enable analyses previously impractical or impossible with conventional titrations and assays. This work significantly broadens the applicability of NMR in physical chemistry and chemical biology, offering efficient new tools for characterizing acid–base equilibria and metal–ligand interactions in complex or inhomogeneous systems
Cefalexin use in UK acute pyelonephritis practice: unaddressed challenges in dosing, breakpoints, and clinical evidence
Get PDFWhy disclose? Understanding users’ self-disclosure on hospitality and tourism social networking sites
Get PDFDespite the proven link between user-generated content and the popularity of tourist destinations, research has left relatively unexamined the drivers of members’ self-disclosure on hospitality and tourism social networking sites (SNSs). Such work is important, because studies report that members of hospitality and tourism SNSs update their personal information and interact with other members significantly less than members of more traditional social media platforms. Accordingly, we draw on social exchange theory and self-regulatory theory to develop a theoretical model that connects perceived benefits and costs to self-disclosure in tourism. We add nuance to our model by examining whether these relationships differ across promotions vs. prevention-focused individuals. The model was empirically tested using structural equation modelling with data gathered from 509 members of two popular Chinese hospitality and tourism SNSs. The findings indicate that while reciprocity, popularity, self-presentation, security, and anonymity positively influence users’ self-disclosure on SNSs, privacy risk has a negative influence. Our findings also show differences across members who are promotion versus prevention focused. This study contributes to the existing literature by proposing a holistic model of self-disclosure on social networking sites
Ships of Memory: Navigating Post-Industrial Landscapes and Participant Engagement through Photographic Reflections
No full textThis photo essay presents an approach to post-industrial landscapes through single objects and their motifs. The stimulus for these reflections came from revisiting photographs I took of North Shields Fish Quay, a deindustrialised fishing port in northeast England. The essay combines fieldwork photographs and interviews conducted with the local Association of Retired Fishermen to reveal the material and discursive lingering of ships in North Shields Fish Quay. Drawing on the concept of “surface encounters”, I envision the potential of these industrial objects to intervene between researcher and participant. The essay describes the attentive dialogues that may have emerged between me and the retired fishers through embracing the physicality of these boats rather than what they symbolise. These reflections offer insight for scholars of deindustrialisation and contemporary archaeologists using participant-oriented methods
Engaging elites, ethnographically: studying powerful actors in sustainable finance
No full textAnthropologists have persuasively made a case for critical ethnographic engagement with elites in recent years. This presents multiple challenges including access and interpretative influence. Wealthy elites have enormous power in many domains of life, not least because of the idea that they “make the world a better place” when they invest their money. Drawing on experiences as someone who first worked in sustainable finance, and who has subsequently undertaken multiple case studies into it, I describe different strategies for ethnographic engagement with powerful financial actors that I have adopted. I propose that what are often derided as “applied goals” of research can help to forge collaborations that enable new forms of participant observation. These can generate original theoretical insights, furthering critical analysis of powerful actors in sustainable finance