People with dry age-related macular degeneration; views on certification of vision impairment in a primary care setting: An explorative qualitative study.

PURPOSE: Evidence supports the clinical decision-making ability of primary care optometrists with additional qualifications in the identification of eligibility criteria for the certification of vision impairment (CVI). Welsh Government policy is driving pathway change to enable these optometrists to perform CVI. This qualitative study explores the views of people with VI due to dry age-related macular degeneration (AMD) on this pathway change. METHODS: Nine people with VI due to dry AMD, attending Macular Society support groups, participated. Individual semi-structured interviews were conducted and analysed concurrently using thematic analysis. RESULTS: Five major themes were identified: (1) living with dry AMD, (2) experience of eye care provision, (3) knowledge of CVI, (4) provision of information and (5) CVI in primary care. Participants consistently highlighted the need for the provision of accessible information regarding the certification pathway, dry AMD and the optometrist's role in the provision of eye health care. Information needs to be available prior to the diagnosis of an eye disease, rather than only from the point of diagnosis or where the vision reaches the level required for certification. CONCLUSION: The findings support the provision of CVI within primary eye care while highlighting areas of importance in pathway development. These include the provision of accessible information prior to, at the point of and following the diagnosis of an eye condition. Information provided needs to extend to the awareness of the role of the optometrist in the provision of eye care, and public health awareness of modifiable risk factors, which will influence the possibility of disease development in later life. The findings provide information that will be useful to those responsible for the provision of CVI within primary care.

Genomic Surveillance of a Globally Circulating Distinct Group W Clonal Complex 11 Meningococcal Variant, New Zealand, 2013-2018.

Genomic surveillance is an essential part of effective disease control, enabling identification of emerging and expanding strains and monitoring of subsequent interventions. Whole-genome sequencing was used to analyze the genomic diversity of all Neisseria meningitidis isolates submitted to the New Zealand Meningococcal Reference Laboratory during 2013-2018. Of the 347 isolates submitted for whole-genome sequencing, we identified 68 sequence types belonging to 18 clonal complexes (CC). The predominant CC was CC41/44; next in predominance was CC11. Comparison of the 45 New Zealand group W CC11 isolates with worldwide representatives of group W CC11 isolates revealed that the original UK strain, the 2013 UK strain, and a distinctive variant (the 2015 strain) were causing invasive group W meningococcal disease in New Zealand. The 2015 strain also demonstrated increased resistance to penicillin and has been circulating in Canada and several countries in Europe, highlighting that close monitoring is needed to prevent future outbreaks around the world.

Victorian Lung Cancer Service Redesign Project: impacts of a quality improvement collaborative on timeliness and management in lung cancer.

BACKGROUND: Lung cancer management is characterised by a high disease burden, poor survival and substantial variation in management and outcomes. Service redesign provides opportunities for quality improvement (QI) and this improvement may be leveraged across multiple sites using QI collaboration. AIM: This initiative targeted Quality Improvement (QI) in lung cancer management, engaging a QI collaborative using service redesign methodologies in five Victorian hospitals. QI targets included timeliness from referral and diagnosis to treatment, multi-disciplinary meeting (MDM) presentation and supportive care screening. Redesign strategies targeted process sustainability through enhanced team capability. METHODS: This study engaged a prospective quality improvement cohort design targeting newly diagnosed tissue confirmed lung cancer with 6-month pre-intervention period and 6-month redesign implementation period, between September 2016 and August 2017, evaluated using Interrupted Time Series Analysis. Hospital sites included three regional and two metropolitan hospitals in Victoria. QI redesign targeted time intervals from referral to first specialist appointment (FSA), referral to diagnosis, diagnosis to first treatment (any intent), MDM documented in medical records and Supportive Care Screening Tool documented in medical records. RESULTS: There was a marked reduction in referral to FSA interval across all sites, with median (interquartile range) falling from 6 (0-15) to 4 (1-10) days, and proportion seen by a specialist within 14 days increased from 74.3% to 84.2%. The interval between diagnosis and treatment was not substantively changed in the 6-month implementation period. The proportion of subjects with documented presentation to the MDM increased from 61% to 67%. The proportion for which Supportive Care Screening documentation remained low at 26.3% post-intervention. CONCLUSIONS: Data-driven redesign initiatives enable identification and analysis of clinical practice variation and may be utilised to enhance timeliness of cancer care and improve local data service capabilities.

Genomic Surveillance of Methicillin-resistant Staphylococcus aureus: A Mathematical Early Modeling Study of Cost-effectiveness.

BACKGROUND: Genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) identifies unsuspected transmission events and outbreaks. Used proactively, this could direct early and highly targeted infection control interventions to prevent ongoing spread. Here, we evaluated the cost-effectiveness of this intervention in a model that compared whole-genome sequencing plus current practice versus current practice alone. METHODS: A UK cost-effectiveness study was conducted using an early model built from the perspective of the National Health Service and personal social services. The effectiveness of sequencing was based on the relative reduction in total MRSA acquisitions in a cohort of hospitalized patients in the year following their index admissions. A sensitivity analysis was used to illustrate and assess the level of confidence associated with the conclusions of our economic evaluation. RESULTS: A cohort of 65 000 patients were run through the model. Assuming that sequencing would result in a 90% reduction in MRSA acquisition, 290 new MRSA cases were avoided. This gave an absolute reduction of 28.8% and avoidance of 2 MRSA-related deaths. Base case results indicated that the use of routine, proactive MRSA sequencing would be associated with estimated cost savings of over £728 290 per annual hospitalized cohort. The impact in total quality-adjusted life years (QALYs) was relatively modest, with sequencing leading to an additional 14.28 QALYs gained. Results were most sensitive to changes in the probability of a MRSA-negative patient acquiring MRSA during their hospital admission. CONCLUSIONS: We showed that proactive genomic surveillance of MRSA is likely to be cost-effective. Further evaluation is required in the context of a prospective study.

Cost-effectiveness of a bacterial-binding dressing to prevent surgical site infection following caesarean section.

OBJECTIVE: A randomised controlled trial (RCT) recruited women undergoing caesarean section (CS) in Poland. The aim of the trial was to assess the efficacy of a dialkylcarbamoyl chloride (DACC)-impregnated surgical dressing (bacterial-binding dressings) compared with standard of care (SoC) in preventing surgical site infection (SSI). The aim of the present analysis was to evaluate the cost-effectiveness of the bacterial-binding dressings in the context of the UK National Health Service (NHS). METHOD: The clinical trial randomised patients to a bacterial-binding dressing (n=272) or a standard surgical dressing (n=271). The study recorded the presence of SSI and associated resource use up to 14 days postoperatively. To generalise results to the NHS, UK unit costs were applied to resource use recorded in the trial. An alternative approach applied a single UK-specific episode cost per SSI. RESULTS: There were 543 women recruited to the trial. SSI rates were 5/272 (1.8%) and 14/271 (5.2%) for bacterial-binding dressings and SoC, respectively (p=0.04). Patients in the bacterial-binding dressing group had six fewer outpatient visits and 33 fewer hospital bed-days. The mean length of SSI-attributable hospitalisation was 2.36 days. Applying UK unit costs at 2017 prices to resource use recorded in the trial, costs of SSI prophylaxis and treatment were £48.97 and £24.69 per patient in the SoC and bacterial-binding dressing groups respectively, a difference of £24.27 (49.6%) per patient. The alternative costing approach produced a cost saving of £119 (57.6%) per patient with the bacterial-binding dressing. CONCLUSION: Use of bacterial-binding dressings following CS has the potential to reduce the incidence of SSI and costs to the NHS.

Elastohydrodynamic Lift at a Soft Wall.

We study experimentally the motion of nondeformable microbeads in a linear shear flow close to a wall bearing a thin and soft polymer layer. Combining microfluidics and 3D optical tracking, we demonstrate that the steady-state bead-to-surface distance increases with the flow strength. Moreover, such lift is shown to result from flow-induced deformations of the layer, in quantitative agreement with theoretical predictions from elastohydrodynamics. This study thus provides the first experimental evidence of "soft lubrication" at play at small scale, in a system relevant, for example, to the physics of blood microcirculation.

Secondary Structure and Glycosylation of Mucus Glycoproteins by Raman Spectroscopies.

The major structural components of protective mucus hydrogels on mucosal surfaces are the secreted polymeric gel-forming mucins. The very high molecular weight and extensive O-glycosylation of gel-forming mucins, which are key to their viscoelastic properties, create problems when studying mucins using conventional biochemical/structural techniques. Thus, key structural information, such as the secondary structure of the various mucin subdomains, and glycosylation patterns along individual molecules, remains to be elucidated. Here, we utilized Raman spectroscopy, Raman optical activity (ROA), circular dichroism (CD), and tip-enhanced Raman spectroscopy (TERS) to study the structure of the secreted polymeric gel-forming mucin MUC5B. ROA indicated that the protein backbone of MUC5B is dominated by unordered conformation, which was found to originate from the heavily glycosylated central mucin domain by isolation of MUC5B O-glycan-rich regions. In sharp contrast, recombinant proteins of the N-terminal region of MUC5B (D1-D2-D'-D3 domains, NT5B), C-terminal region of MUC5B (D4-B-C-CK domains, CT5B) and the Cys-domain (within the central mucin domain of MUC5B) were found to be dominated by the ß-sheet. Using these findings, we employed TERS, which combines the chemical specificity of Raman spectroscopy with the spatial resolution of atomic force microscopy to study the secondary structure along 90 nm of an individual MUC5B molecule. Interestingly, the molecule was found to contain a large amount of α-helix/unordered structures and many signatures of glycosylation, pointing to a highly O-glycosylated region on the mucin.

Role of caspases in cytokine-induced barrier breakdown in human brain endothelial cells.

During neuroinflammation, cytokines such as TNF-α and IFN-γ secreted by activated leukocytes and/or CNS resident cells have been shown to alter the phenotype and function of brain endothelial cells (BECs) leading to blood-brain barrier breakdown. In this study, we show that the human BEC line hCMEC/D3 expresses the receptors for TNF-α, TNF receptor 1 and TNF receptor 2, and for IFN-γ. BEC activation with TNF-α alone or in combination with IFN-γ induced endothelial leakage of paracellular tracers. At high cytokine concentrations (10 and 100 ng/ml), this effect was associated with caspase-3/7 activation and apoptotic cell death as evidenced by annexin V staining and DNA fragmentation (TUNEL) assays. In addition, inhibition of JNK and protein kinase C activation at these doses partially prevented activation of caspase-3/7, although only JNK inhibition was partially able to prevent the increase in BEC paracellular permeability induced by cytokines. By contrast, lower cytokine concentrations (1 ng/ml) also led to effector caspase activation, increased paracellular flux, and redistribution of zonula occludens-1 and VE-cadherin but failed to induce apoptosis. Under these conditions, specific caspase-3 and caspase-9, but not caspase-8, inhibitors partially blocked cytokine-induced disruption of tight and adherens junctions and BEC paracellular permeability. Our results suggest that the concentration of cytokines in the CNS endothelial microenvironment determines the extent of caspase-mediated barrier permeability changes, which may be generalized as a result of apoptosis or more subtle as a result of alterations in the organization of junctional complex molecules.

Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition.

Stress has been identified as a major causal factor for many mental disorders. However, our knowledge about the chain of molecular and cellular events translating stress experience into altered behavior is still rather scant. Here, we have characterized a murine ortholog of the putative tumor suppressor gene DRR1 as a unique stress-induced protein in brain. It binds to actin, promotes bundling and stabilization of actin filaments, and impacts on actin-dependent neurite outgrowth. Endogenous DRR1 localizes to some, but not all, synapses, with preference for the presynaptic region. Hippocampal virus-mediated enhancement of DRR1 expression reduced spine density, diminished the probability of synaptic glutamate release, and altered cognitive performance. DRR1 emerges as a protein to link stress with actin dynamics, which in addition is able to act on synaptic function and cognition.

Evaluating ChatGPT text mining of clinical records for companion animal obesity monitoring.

BACKGROUND: Veterinary clinical narratives remain a largely untapped resource for addressing complex diseases. Here we compare the ability of a large language model (ChatGPT) and a previously developed regular expression (RegexT) to identify overweight body condition scores (BCS) in veterinary narratives pertaining to companion animals. METHODS: BCS values were extracted from 4415 anonymised clinical narratives using either RegexT or by appending the narrative to a prompt sent to ChatGPT, prompting the model to return the BCS information. Data were manually reviewed for comparison. RESULTS: The precision of RegexT was higher (100%, 95% confidence interval [CI] 94.81%-100%) than that of ChatGPT (89.3%, 95% CI 82.75%-93.64%). However, the recall of ChatGPT (100%, 95% CI 96.18%-100%) was considerably higher than that of RegexT (72.6%, 95% CI 63.92%-79.94%). LIMITATIONS: Prior anonymisation and subtle prompt engineering are needed to improve ChatGPT output. CONCLUSIONS: Large language models create diverse opportunities and, while complex, present an intuitive interface to information. However, they require careful implementation to avoid unpredictable errors.

Text mining for disease surveillance in veterinary clinical data: part one, the language of veterinary clinical records and searching for words.

The development of natural language processing techniques for deriving useful information from unstructured clinical narratives is a fast-paced and rapidly evolving area of machine learning research. Large volumes of veterinary clinical narratives now exist curated by projects such as the Small Animal Veterinary Surveillance Network (SAVSNET) and VetCompass, and the application of such techniques to these datasets is already (and will continue to) improve our understanding of disease and disease patterns within veterinary medicine. In part one of this two part article series, we discuss the importance of understanding the lexical structure of clinical records and discuss the use of basic tools for filtering records based on key words and more complex rule based pattern matching approaches. We discuss the strengths and weaknesses of these approaches highlighting the on-going potential value in using these "traditional" approaches but ultimately recognizing that these approaches constrain how effectively information retrieval can be automated. This sets the scene for the introduction of machine-learning methodologies and the plethora of opportunities for automation of information extraction these present which is discussed in part two of the series.

myCOPD App for Managing Chronic Obstructive Pulmonary Disease: A NICE Medical Technology Guidance for a Digital Health Technology.

myCOPD is a digital tool designed for people to manage their chronic obstructive pulmonary disease (COPD). It requires a device with an internet connection and incorporates tools for education, self-management, symptom tracking and pulmonary rehabilitation (PR). myCOPD was selected for medical technologies guidance by the UK National Institute for Health and Care Excellence (NICE) in 2020. The External Assessment Group (EAG) critiqued the company's submission. The evidence comprised four clinical studies (three randomised controlled trials [RCTs] and one observational study) and real-world evidence from 22 documents. The RCTs had small sample sizes, limiting the power to detect statistically significant differences and to match patient characteristics across arms. The company produced two de novo models for two subgroups of people with COPD; people discharged from hospital with acute exacerbation of COPD (AECOPD) and people referred for PR. After the EAG updated input parameters and adjusted the model structures, cost savings of £86,297 per clinical commissioning group (CCG) compared with standard care were estimated for the AECOPD population, with myCOPD predicted to be cost saving in 74% of iterations. Cost savings of £22,779 per CCG were estimated for the PR population (with the assumption that the CCG had an existing myCOPD licence), with myCOPD predicted to be cost saving in 86% of the iterations. The Medical Technologies Advisory Committee concluded that although myCOPD has the potential to help manage COPD in adults, further evidence is required to address uncertainties in the current evidence base. NICE published this as Medical Technology Guidance 68 (National Institute for Health and Care Excellence (NICE). myCOPD for managing chronic obstructive pulmonary disease. 2022. Available at: https://www.nice.org.uk/guidance/mtg68/ ).

Transarterial therapies in patients with hepatocellular carcinoma eligible for transarterial embolization: a US cost-effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC). DESIGN: A cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a "watch and wait" state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature. RESULTS: At five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained. CONCLUSIONS: TARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators.

The Barcelona Clinic Liver Cancer guideline recommends the use of transarterial radioembolization (TARE), conventional (cTACE), or drug-eluting bead transarterial chemoembolization (DEE-TACE) for treating hepatocellular carcinoma (HCC). This study evaluated the cost-effectiveness of TARE versus two alternative embolization treatments (cTACE and DEE-TACE) in treating patients with unresectable early- to intermediate-stage HCC.A cohort-based Markov model was developed to analyze the costs and benefits of these treatments from a US healthcare perspective within a 5-year time horizon. A 20-year time horizon was assessed as a scenario. In the model, patients were assigned to receive TARE, cTACE, or DEE-TACE and remained in the "watch and wait" stage for tumor downstaging. Data used in the model was taken from previous studies and in consultation with clinical experts. The benefits of the treatments were measured by considering the impact on the patient's quality of life. The costs associated with the treatments were obtained from various sources, including reports, publicly available databases, and published literature.The findings show that TARE is not only cost-saving compared to cTACE but also results in a higher number of quality-adjusted life years (QALYs) per person. While TARE was more expensive than DEE-TACE, it produced more QALYs, further indicating more favorable patient outcomes and overall treatment effectiveness. These findings could potentially impact resource allocation and decision-making for the treatment of HCC.

Developing a Modeling Framework for Quantifying the Health and Cost Implications of Antibiotic Resistance for Surgical Procedures.

Background. Antimicrobial resistance (AMR) is a global public health threat. The wider implications of AMR, such as the impact of antibiotic resistance (ABR) on surgical procedures, are yet to be quantified. The objective of this study was to produce a conceptual modeling framework to provide a basis for estimating the current and potential future consequences of ABR for surgical procedures in England. Design. A framework was developed using literature-based evidence and structured expert elicitation. This was applied to populations undergoing emergency repair of the neck of the femur and elective colorectal resection surgery. Results. The framework captures the implications of increasing ABR by allowing for higher rates of surgical site infection (SSI) as the effectiveness of antibiotic prophylaxis wanes and worsened outcomes following SSIs to reflect reduced antibiotic treatment effectiveness. The expert elicitation highlights the uncertainty in quantifying the impact of ABR, reflected in the results. A hypothetical SSI rate increase of 14% in a person undergoing emergency repair of the femur could increase costs by 39% (-2% to 108% credible interval [CI]) and decrease quality-adjusted life-years by 11% (0.4% to 62% CI) over 15 y. Conclusions. The modeling framework is a starting point for addressing the implication of ABR on the outcomes and costs of surgeries. Due to clinical uncertainty highlighted in the expert elicitation process, the numerical outputs of the case studies should not be focused on but rather the framework itself, illustration of the evidence gaps, the benefit of expert elicitation in quantifying parameters with limited data, and the potential magnitude of the impact of ABR on surgical procedures. Implications. The framework can be used to support research surrounding the health and cost burden of ABR in England. Highlights: The modeling framework is a starting point for assessing the health and cost impacts of antibiotic resistance on surgeries in England.Formulating a framework and synthesizing evidence to parameterize data gaps provides targets for future research.Once data gaps are addressed, this modeling framework can be used to feed into overall estimates of the health and cost burden of antibiotic resistance and evaluate control policies.

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.

Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL.

Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of aging. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesized from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to 'restore' cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial 'support' at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD-95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction.

Evaluation of the Cost-Utility of the York Faecal Calprotectin Care Pathway.

Background: Lower gastrointestinal symptoms are common in the general population and it can be difficult to discriminate between inflammatory bowel disease (IBS) and irritable bowel syndrome (IBD) due to overlap of symptoms. The York Fecal Calprotectin Care Pathway (YFCCP) was introduced in 2016 as an alternative to the NICE fecal calprotectin pathway (DG11). This analysis uses the prospective data from the first 1005 patients in the YFCCP. Previous analysis demonstrated the YFCCP may be cost-saving when compared with the DG11 pathway. This analysis examined the short-term health-related quality of life (HRQoL) impact for patients in the YFCCP for IBD and IBS.Methods: A decision tree model was used to estimate the proportion of people presenting with lower gastrointestinal symptoms that were correctly or falsely diagnosed with IBS and IBD. Time to diagnosis data was estimated and HRQoL data was estimated from published sources. Costs and QALYs were calculated for the YFCCP and each comparator.Results: The YFCCP was cost-effective at a £20,000 threshold when compared with the current NICE recommended pathways and was cost-saving with a QALY gain (dominant)in four of the five comparators. Conclusions: The YFCCP demonstrated a QALY benefit when compared with all alternative pathways.

Comparative genomics of Bordetella pertussis isolates from New Zealand, a country with an uncommonly high incidence of whooping cough.

Whooping cough, the respiratory disease caused by Bordetella pertussis, has undergone a wide-spread resurgence over the last several decades. Previously, we developed a pipeline to assemble the repetitive B. pertussis genome into closed sequences using hybrid nanopore and Illumina sequencing. Here, this sequencing pipeline was used to conduct a more high-throughput, longitudinal screen of 66 strains isolated between 1982 and 2018 in New Zealand. New Zealand has a higher incidence of whooping cough than many other countries; usually at least twice as many cases per 100000 people as the USA and UK and often even higher, despite similar rates of vaccine uptake. To the best of our knowledge, these strains are the first New Zealand B. pertussis isolates to be sequenced. The analyses here show that, on the whole, genomic trends in New Zealand B. pertussis isolates, such as changing allelic profile in vaccine-related genes and increasing pertactin deficiency, have paralleled those seen elsewhere in the world. At the same time, phylogenetic comparisons of the New Zealand isolates with global isolates suggest that a number of strains are circulating in New Zealand, which cluster separately from other global strains, but which are closely related to each other. The results of this study add to a growing body of knowledge regarding recent changes to the B. pertussis genome, and are the first genetic investigation into B. pertussis isolates from New Zealand.

UK veterinary professionals' perceptions and experiences of adverse drug reaction reporting.

BACKGROUND: Spontaneous reporting of suspected adverse drug reactions (ADRs) is the cornerstone of pharmacovigilance. Despite this, it is believed that there is significant under-reporting in the veterinary setting. Low reporting rates delay marketing authorisation holders (MAHs) and regulators taking mitigating action in the case of safety concerns. METHOD: We designed a survey to explore the perceptions, attitudes and experiences of UK veterinary professionals towards ADR reporting. The survey was advertised widely through conventional and social media and at several conferences. RESULTS: In total, 260 respondents completed the survey, including 210 veterinary surgeons, 49 veterinary nurses and one suitably qualified person. Respondents generally understood the need to report ADRs. The main barrier to reporting was the suspected ADR being well known, and the most popular potential facilitator identified was the ability to report via the practice management system. Facilitation via education in the form of a pharmacovigilance themed continuing professional development event was particularly popular among veterinary nurses, who reported time as being less of a barrier to reporting than their veterinary surgeon counterparts. CONCLUSIONS: Our findings suggest that technological interventions to facilitate reporting and empowerment of veterinary nurses to report through a tailored training event should be explored further.

Estimating the time involved in managing the 'unoccupied bed:' a time and motion study.

Occupied bed days are often used as a demand indicator when calculating the number of nurses required to provide safe care. However, such calculations fail to take into account the amount of nursing time consumed by the "unoccupied bed." This study used direct observation time-and-motion methods to estimate the time and costs associated with a bed that is unoccupied. The average time taken to complete all of the activities associated with a bed that was unoccupied due to an internal transfer was 8.65 minutes, for a patient discharge 26.27 minutes, and for a patient admission 37.7 minutes. An average daily cost for activities surrounding these patient movements was approximately $386/day (AUD) in registered/enrolled nursing salaries alone. The unoccupied bed is not resource neutral and time associated with its maintenance should be considered when calculating nursing requirements to provide safe care.