Implementation and evaluation of a SARI surveillance system in a tertiary hospital in Scotland in 2021/2022.

OBJECTIVE: To set up and evaluate a new surveillance system for severe acute respiratory infection (SARI) in Scotland. STUDY DESIGN: Cross-sectional study and evaluation of surveillance system. METHODS: The SARI case definition comprised patients aged 16 years or over with an acute respiratory illness presentation requiring testing for influenza and SARS-CoV-2 and hospital admission. Data were collected from SARI cases by research nurses in one tertiary teaching hospital using a bespoke data collection tool from November 2021 to May 2022. Descriptive analyses of SARI cases were carried out. The following attributes of the surveillance system were evaluated according to Centers for Disease Control and Prevention (CDC) guidelines: stability, data quality, timeliness, positive predictive value, representativeness, simplicity, acceptability and flexibility. RESULTS: The final surveillance dataset comprised 1163 records, with cases peaking in ISO week 50 (week ending 19/12/2021). The system produced a stable stream of surveillance data, with the proportion of SARI records with sufficient information for effective surveillance increasing from 65.4% during the first month to 87.0% over time. Similarly, the proportion where data collection was completed promptly was low initially, but increased to 50%-65% during later periods. CONCLUSION: SARI surveillance was successfully established in one hospital, but for a national system, additional sentinel hospital sites across Scotland, with flexibility to ensure consistently high data completeness and timeliness are needed. Data collection should be automated where possible, and demands on clinicians minimised. SARI surveillance should be embedded and resourced as part of a national respiratory surveillance strategy.

Real-time surveillance of severe acute respiratory infections in Scottish hospitals: an electronic register-based approach, 2017-2022.

OBJECTIVES: The COVID-19 pandemic highlighted the importance of routine syndromic surveillance of respiratory infections, specifically new cases of severe acute respiratory infection (SARI). This surveillance often relies on questionnaires carried out by research nurses or transcriptions of doctor's notes, but existing, routinely collected electronic healthcare data sets are increasingly being used for such surveillance. We investigated how patient diagnosis codes, recorded within such data sets, could be used to capture SARI trends in Scotland. STUDY DESIGN: We conducted a retrospective observational study using electronic healthcare data sets between 2017 and 2022. METHODS: Sensitive, specific and timely case definition (CDs) based on patient diagnosis codes contained within national registers in Scotland were proposed to identify SARI cases. Representativeness and sensitivity analyses were performed to assess how well SARI cases captured by each definition matched trends in historic influenza and SARS-CoV-2 data. RESULTS: All CDs accurately captured the peaks seen in laboratory-confirmed positive influenza and SARS-CoV-2 data, although the completeness of patient diagnosis records was discovered to vary widely. The timely CD provided the earliest detection of changes in SARI activity, whilst the sensitive CD provided insight into the burden and severity of SARI infections. CONCLUSIONS: A universal SARI surveillance system has been developed and demonstrated to accurately capture seasonal SARI trends. It can be used as an indicator of emerging secondary care burden of emerging SARI outbreaks. The system further strengthens Scotland's existing strategies for respiratory surveillance, and the methods described here can be applied within any country with suitable electronic patient records.

Symptoms of lumbar spinal stenosis in people with knee or hip osteoarthritis or low back pain: a cross-sectional study of 10,234 participants in primary care.

OBJECTIVE: The aims of this study were to evaluate: the proportion of people reporting symptoms associated with lumbar spinal stenosis (LSS) in primary care programs for knee or hip osteoarthritis (OA) or persistent low back pain (LBP) and; the prevalence of self-reported clinical LSS in these three cohorts, according to two sets of adapted criteria. METHOD: A cross-sectional analysis of baseline data from the Good Life with osteoArthritis in Denmark primary care programs. Self-report LSS symptom questions were administered to participants with knee OA, hip OA, and persistent LBP. The prevalence of eleven LSS symptoms and clinical LSS were calculated for each cohort. RESULTS: A total of 10,234 participants were included in the analysis. A similar proportion of participants in each cohort were female (69%), with a 6- and 7-year older mean age in the knee and hip cohorts compared to the back cohort. A greater proportion of participants with LBP reported LSS symptoms (range 11-71%) than in the hip (11-50%) and knee (8-40%) cohorts. This pattern was observed for all but one symptom. The same pattern was observed for the prevalence of clinical LSS with less than 10% of people in each cohort satisfying the clinical criteria. CONCLUSION: Self-reported LSS symptoms are commonly reported by people treated in primary care for knee or hip OA, although not as frequently as reported by those with LBP. Despite symptoms of LSS being common, only a small proportion of people were classified as having self-reported clinical LSS.

Trimethyl chitosan-capped silver nanoparticles with positive surface charge: Their catalytic activity and antibacterial spectrum including multidrug-resistant strains of Acinetobacter baumannii.

We report a facile route for the green synthesis of trimethyl chitosan nitrate-capped silver nanoparticles (TMCN-AgNPs) with positive surface charge. In this synthesis, silver nitrate, glucose, and trimethyl chitosan nitrate (TMCN) were used as silver precursor, reducing agent, and stabilizer, respectively. The reaction was carried out in a stirred basic aqueous medium at room temperature without the use of energy-consuming or expensive equipment. We investigated the effects of the concentrations of NaOH, glucose, and TMCN on the particle size, zeta potential, and formation yield. The AgNPs were characterized by UV-vis spectroscopy, photon correlation spectroscopy, laser Doppler anemometry, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The catalytic activity of the TMCN-AgNPs was studied by the reduction of 4-nitrophenol using NaBH4 as a reducing agent. We evaluated the antibacterial effects of the TMCN-AgNPs on Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the broth microdilution method. The results showed that both gram-positive and gram-negative bacteria were killed by the TMCN-AgNPs at very low concentration (<6.13µg/mL). Moreover, the TMCN-AgNPs also showed high antibacterial activity against clinically isolated multidrug-resistant A. baumannii strains, and the minimum inhibitory concentration (MIC) was ≤12.25µg/mL.

Bristles reduce the force required to 'fling' wings apart in the smallest insects.

The smallest flying insects commonly possess wings with long bristles. Little quantitative information is available on the morphology of these bristles, and their functional importance remains a mystery. In this study, we (1) collected morphological data on the bristles of 23 species of Mymaridae by analyzing high-resolution photographs and (2) used the immersed boundary method to determine via numerical simulation whether bristled wings reduced the force required to fling the wings apart while still maintaining lift. The effects of Reynolds number, angle of attack, bristle spacing and wing-wing interactions were investigated. In the morphological study, we found that as the body length of Mymaridae decreases, the diameter and gap between bristles decreases and the percentage of the wing area covered by bristles increases. In the numerical study, we found that a bristled wing experiences less force than a solid wing. The decrease in force with increasing gap to diameter ratio is greater at higher angles of attack than at lower angles of attack, suggesting that bristled wings may act more like solid wings at lower angles of attack than they do at higher angles of attack. In wing-wing interactions, bristled wings significantly decrease the drag required to fling two wings apart compared with solid wings, especially at lower Reynolds numbers. These results support the idea that bristles may offer an aerodynamic benefit during clap and fling in tiny insects.

Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS-induced DNA damage and premature senescence.

Approximately 20% of tumors contain activating mutations in the RAS family of oncogenes. As tumors progress to higher grades of malignancy, the expression of oncogenic RAS has been reported to increase, leading to an oncogene-induced senescence (OIS) response. Evasion of this senescence barrier is a hallmark of advanced tumors indicating that OIS serves a critical tumor-suppressive function. Induction of OIS has been attributed to either RAS-mediated production of reactive oxygen species (ROS) or to induction of a DNA damage response (DDR). However, functional links between these two processes in triggering the senescent phenotype have not been explicitly described. Our previous work has shown that, in cultured untransformed cells, preventing elimination of oxidized guanine deoxyribonucleotides, which was achieved by suppressing expression of the cellular 8-oxo-dGTPase, human MutT homolog 1 (MTH1), sufficed to induce a DDR as well as premature senescence. Here, we demonstrate that overexpression of MTH1 can prevent the oncogenic H-RAS-induced DDR and attendant premature senescence, although it does not affect the observed elevation in ROS levels produced by RAS oncoprotein expression. Conversely, we find that loss of MTH1 preferentially induces an in vitro proliferation defect in tumorigenic cells overexpressing oncogenic RAS. These results indicate that the guanine nucleotide pool is a critical target for intracellular ROS produced by oncogenic RAS and that RAS-transformed cells require robust MTH1 expression to proliferate.

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene.

Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI scaffolding proteins as ERBB4-binding proteins. After validating the interaction of MAGI proteins with ERBB4 in mammalian cells, we demonstrated that ERBB4 expression, alone or in combination with ERBB2 or ERBB3, led to the tyrosine phosphorylation of MAGI proteins, and that this could be further enhanced with receptor activation by neuregulin. As MAGI proteins were previously shown to interact with receptor phosphotyrosine phosphatase beta/zeta (RPTPbeta), we postulated that simultaneous binding of MAGI proteins to RPTPbeta and ERBB4 forms a phosphotyrosine kinase/phosphotyrosine phosphatase complex. Studies in cultured cells confirmed both a spatial and functional association between ERBB4, MAGI and RPTPbeta. Given the evidence for this functional association, we examined the genes coding for MAGI and RPTPbeta for genetic association with schizophrenia in a Caucasian United Kingdom case-control cohort (n= approximately 1400). PTPRZ1, which codes for RPTPbeta, showed significant, gene-wide and hypothesis-wide association with schizophrenia in our study (best individual single-nucleotide polymorphism allelic P=0.0003; gene-wide P=0.0064; hypothesis-wide P=0.026). The data provide evidence for a role of PTPRZ1, and for RPTPbeta signaling abnormalities, in the etiology of schizophrenia. Furthermore, the data indicate a role for RPTPbeta in the modulation of ERBB4 signaling that may in turn provide further support for an important role of neuregulin/ERBB4 signaling in the molecular basis of schizophrenia.

Decision threshold adjustment in class prediction.

Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations.

Quantitative density profiling with pure phase encoding and a dedicated 1D gradient.

A new centric scan imaging methodology for density profiling of materials with short transverse relaxation times is presented. This method is shown to be more robust than our previously reported centric scan pure phase encode methodologies. The method is particularly well suited to density imaging of low gyro-magnetic ratio non-proton nuclei through the use of a novel dedicated one-dimensional magnetic field gradient coil. The design and construction of this multi-layer, water cooled, gradient coil is presented. Although of large diameter (7.62 cm) to maximize sample cross section, the gradient coil has an efficiency of several times that offered by conventional designs (6 mT/m/A). The application of these ideas is illustrated with high resolution density-weighted proton (1H) images of hazelnut oil penetration into chocolate, and lithium ion (7Li) penetration into cement paste. The methods described in this paper provide a straightforward and reliable means for imaging a class of samples that, until now, have been very difficult to image.

Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban.

BACKGROUND: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported. METHODS/RESULTS: We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition. CONCLUSION: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.

Abciximab: cost-effective survival advantage in clinical trials and clinical practice.

Adjunctive blockade of the platelet glycoprotein (GP) IIb/IIIa receptor during either percutaneous coronary intervention (PCI) or for patients who present with non-ST segment elevation acute coronary syndromes has demonstrated efficacy in reducing platelet-mediated adverse cardiovascular ischemic events. The three currently available agents (abciximab, eptifibatide, tirofiban) differ markedly in pharmacodynamic and pharmacokinetic profiles, receptor affinity, and cost. Although pharmacoeconomic substudies are available from placebo-controlled randomized trials of platelet GPIIb/IIIa blockade during PCI, "real-world" cost-effectiveness data from high-volume practice are lacking. Therefore, in-hospital and late (6-month) clinical outcomes and cumulative cost/charge data were analyzed on 1472 consecutive PCI procedures (70% received abciximab) performed by high-volume operators at a single institution.(1) Data were adjusted for lack of randomized treatment allocation with the use of a propensity scoring technique. Adjunctive abciximab therapy for PCI was associated with a significant (3.4%) reduction in mortality to 6 months. Based on the economic cost-effectiveness concept of cost per life year gained relative to standard therapy,(2,3) abciximab provided a cost-effective survival advantage in high-volume interventional practice that compares very favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness include multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction (MI), and impaired left-ventricular (LV) function.

Low-molecular-weight heparin therapy in percutaneous coronary intervention: the NICE 1 and NICE 4 trials. National Investigators Collaborating on Enoxaparin Investigators.

Early coronary intervention in patients with non-ST segment elevation acute coronary syndromes (ACS) may be facilitated by adjunctive pharmacotherapies. Concomitant therapies such as low-molecular-weight heparins and platelet glycoprotein (GP) IIb/IIIa receptor blockade offer advantages in safety and efficacy during coronary intervention. Data from randomized clinical trials support the administration of both enoxaparin and platelet GP IIb/IIIa blockade to patients who present with non-ST segment elevation ACS. Enoxaparin, with its proven efficacy, predictability of action, and ease of administration, has been shown to be superior to unfractionated heparin in preventing major coronary events. Abciximab administration during percutaneous coronary intervention (PCI) reduces the incidence of ischemic adverse outcomes and appears to improve survival in long-term follow-up. The preliminary experience with combining these two therapies during PCI in the NICE 4 trial demonstrates a low incidence of minor/major bleeding and transfusion, and infrequent major cardiac events to 30 days follow-up. Algorithms for the use of these newer adjunctive pharmacotherapies in the care of patients presenting to the cardiac catheterization laboratory are presented.

The effect of food on the pharmacokinetics of the bicalutamide ('Casodex') enantiomers.

'Casodex' (bicalutamide) is an orally active, non-steroidal, pure antiandrogen; it is a racemate with antiandrogenic activity residing predominantly in the (R)-enantiomer. Healthy male volunteers (n = 15) were administered single oral doses of bicalutamide (50 mg) after food and after fasting as part of a three-treatment, three-period, randomized cross-over study, with a 9 week washout. After fasting, plasma concentrations of (R)-bicalutamide were much higher than those of (S)-bicalutamide; the mean (R)-enantiomer Cmax (734 ng mL-1) was about nine times higher than the (S)-enantiomer value (84 ng mL-1). The corresponding tmax values were 19 and 3 h for (R)- and (S)-bicalutamide, respectively. Elimination of (R)-bicalutamide from plasma was monoexponential and slow (t1/2 = 5.8 d). Elimination of (S)-bicalutamide was biphasic in some volunteers but monophasic in others (terminal t1/2 =1.2 d; n = 11). There was no significant effect of food on AUC, tmax, or t1/2 data for either enantiomer. The observed slightly higher values of Cmax for (R)-bicalutamide (14%) and (S)-bicalutamide (19%), when dosing with food, achieved statistical significance. However, differences of this magnitude are unlikely to to be of any clinical relevance. These data indicate that 'Casodex' can be taken without reference to meal times; this may be of particular relevance for its indication in a disease of the elderly.