Non-pharmaceutical interventions to reduce COVID-19 transmission in the UK: a rapid mapping review and interactive evidence gap map.

BACKGROUND: Non-pharmaceutical interventions (NPIs) were crucial in the response to the COVID-19 pandemic, although uncertainties about their effectiveness remain. This work aimed to better understand the evidence generated during the pandemic on the effectiveness of NPIs implemented in the UK. METHODS: We conducted a rapid mapping review (search date: 1 March 2023) to identify primary studies reporting on the effectiveness of NPIs to reduce COVID-19 transmission. Included studies were displayed in an interactive evidence gap map. RESULTS: After removal of duplicates, 11 752 records were screened. Of these, 151 were included, including 100 modelling studies but only 2 randomized controlled trials and 10 longitudinal observational studies.Most studies reported on NPIs to identify and isolate those who are or may become infectious, and on NPIs to reduce the number of contacts. There was an evidence gap for hand and respiratory hygiene, ventilation and cleaning. CONCLUSIONS: Our findings show that despite the large number of studies published, there is still a lack of robust evaluations of the NPIs implemented in the UK. There is a need to build evaluation into the design and implementation of public health interventions and policies from the start of any future pandemic or other public health emergency.

Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Did the UK's public health shielding policy protect the clinically extremely vulnerable during the COVID-19 pandemic in Wales? Results of EVITE Immunity, a linked data retrospective study.

INTRODUCTION: The UK shielding policy intended to protect people at the highest risk of harm from COVID-19 infection. We aimed to describe intervention effects in Wales at 1 year. METHODS: Retrospective comparison of linked demographic and clinical data for cohorts comprising people identified for shielding from 23 March to 21 May 2020; and the rest of the population. Health records were extracted with event dates between 23 March 2020 and 22 March 2021 for the comparator cohort and from the date of inclusion until 1 year later for the shielded cohort. RESULTS: The shielded cohort included 117,415 people, with 3,086,385 in the comparator cohort. The largest clinical categories in the shielded cohort were severe respiratory condition (35.5%), immunosuppressive therapy (25.9%) and cancer (18.6%). People in the shielded cohort were more likely to be female, aged ≥50 years, living in relatively deprived areas, care home residents and frail. The proportion of people tested for COVID-19 was higher in the shielded cohort (odds ratio [OR] 1.616; 95% confidence interval [CI] 1.597-1.637), with lower positivity rate incident rate ratios 0.716 (95% CI 0.697-0.736). The known infection rate was higher in the shielded cohort (5.9% vs 5.7%). People in the shielded cohort were more likely to die (OR 3.683; 95% CI: 3.583-3.786), have a critical care admission (OR 3.339; 95% CI: 3.111-3.583), hospital emergency admission (OR 2.883; 95% CI: 2.837-2.930), emergency department attendance (OR 1.893; 95% CI: 1.867-1.919) and common mental disorder (OR 1.762; 95% CI: 1.735-1.789). CONCLUSION: Deaths and healthcare utilisation were higher amongst shielded people than the general population, as would be expected in the sicker population. Differences in testing rates, deprivation and pre-existing health are potential confounders; however, lack of clear impact on infection rates raises questions about the success of shielding and indicates that further research is required to fully evaluate this national policy intervention.

Colonoscopy skills improvement training improves patient comfort during colonoscopy.

INTRODUCTION: We aimed to assess the effect of Colonoscopy Skills Improvement (CSI) training on patient comfort and sedation-related complications during colonoscopy. METHODS: This retrospective cohort study was performed on 19 endoscopists practicing in a Canadian tertiary care center who completed CSI training between October 2014 and May 2016. Data from 50 procedures immediately prior to, immediately after, and eight months following CSI training were included for each endoscopist. The primary outcome variable was intraprocedural comfort, and secondary outcomes included intraprocedural hypotension and hypoxia. Data were extracted from an electronic medical record and analyzed using SPSS version 20.0. Univariate analysis and stepwise multivariable logistic regression were performed to determine if there was an association between patient comfort and CSI training. Predictors of these outcomes including patient age, gender, sedation use and dosing, procedure completion, quality of bowel preparation, endoscopist experience, and specialty were included in the analysis. RESULTS: 2533 colonoscopies were included in the study. The mean dose of sedatives was reduced immediately following CSI training and at 8 months for both Fentanyl (75.4 mcg v. 67.8 mcg v. 65.9 mcg, p < 0.001) and Midazolam (2.57 mg v. 2.27 mg v. 2.19 mg, p < 0.001). The percentage of patients deemed to have a comfortable exam improved following endoscopist participation in CSI training and remained improved at 8 months (55.1% v. 70.2% v. 69.8%, p < 0.001). No significant change in rates of intraprocedural hypoxia or hypotension were noted following CSI training. CONCLUSION: CSI training is associated with improved patient comfort and reduced sedation requirements during colonoscopy.

Realist analysis of whether emergency departments with primary care services generate 'provider-induced demand'.

BACKGROUND: It is not known whether emergency departments (EDs) with primary care services influence demand for non-urgent care ('provider-induced demand'). We proposed that distinct primary care services in EDs encourages primary care demand, whereas primary care integrated within EDs may be less likely to cause additional demand. We aimed to explore this and explain contexts (C), mechanisms (M) and outcomes (O) influencing demand. METHODS: We used realist evaluation methodology and observed ED service delivery. Twenty-four patients and 106 staff members (including Clinical Directors and General Practitioners) were interviewed at 13 EDs in England and Wales (240 hours of observations across 30 days). Field notes from observations and interviews were analysed by creating 'CMO' configurations to develop and refine theories relating to drivers of demand. RESULTS: EDs with distinct primary care services were perceived to attract demand for primary care because services were visible, known or enabled direct access to health care services. Other influencing factors included patients' experiences of accessing primary care, community care capacity, service design and population characteristics. CONCLUSIONS: Patient, local-system and wider-system factors can contribute to additional demand at EDs that include primary care services. Our findings can inform service providers and policymakers in developing strategies to limit the effect of potential influences on additional demand when demand exceeds capacity.

Fidelity to an evidence-based model for crisis resolution teams: a cross-sectional multicentre study in Norway.

BACKGROUND: Crisis resolution teams (CRTs) are specialized multidisciplinary teams intended to provide assessment and short-term outpatient or home treatment as an alternative to hospital admission for people experiencing a mental health crisis. In Norway, CRTs have been established within mental health services throughout the country, but their fidelity to an evidence-based model for CRTs has been unknown. METHODS: We assessed fidelity to the evidence-based CRT model for 28 CRTs, using the CORE Crisis Resolution Team Fidelity Scale Version 2, a tool developed and first applied in the UK to measure adherence to a model of optimal CRT practice. The assessments were completed by evaluation teams based on written information, interviews, and review of patient records during a one-day visit with each CRT. RESULTS: The fidelity scale was applicable for assessing fidelity of Norwegian CRTs to the CRT model. On a scale 1 to 5, the mean fidelity score was low (2.75) and with a moderate variation of fidelity across the teams. The CRTs had highest scores on the content and delivery of care subscale, and lowest on the location and timing of care subscale. Scores were high on items measuring comprehensive assessment, psychological interventions, visit length, service users' choice of location, and of type of support. However, scores were low on opening hours, gatekeeping acute psychiatric beds, facilitating early hospital discharge, intensity of contact, providing medication, and providing practical support. CONCLUSIONS: The CORE CRT Fidelity Scale was applicable and relevant to assessment of Norwegian CRTs and may be used to guide further development in clinical practice and research. Lower fidelity and differences in fidelity patterns compared to the UK teams may indicate that Norwegian teams are more focused on early interventions to a broader patient group and less on avoiding acute inpatient admissions for patients with severe mental illness.

Quantitative Microbial Risk Assessment (QMRA) of Workers Exposure to Bioaerosols at MSW Open Dumpsites.

The bioaerosol exposure data from the study by Akpeimeh, Fletcher, and Evans (2019) was used to compute the risk of infection from the exposure of dumpsite workers to Aspergillus fumigatus and Escherichia coli O157:H7. A stochastic (Markov Chain) model was used to model the transport of the inhaled dose though the human respiratory system and then integrated into the beta-Poisson dose-response model to estimate workers risks of respiratory and gastrointestinal (GI) infection. The infection risk was computed based on workers exposure to E. coli O157:H7 at 10-50% pathogen ingestion rate and pathogen-indicator ratio (P:I) of 1:103 and 1:104 , while exposure to A. fumigatus was based solely on the average initial exposure dose. The results showed that after 11 hours of exposure, workers engaged in scavenging, waste sorting, and site monitoring were at risk of respiratory and GI infection in the magnitude of 10-1 . However, the risk estimates associated with specific areas of the dumpsite showed that, the risk of GI infection at the active area ranged between 3.23 × 10-3 -1.56 × 10-2 and 3.25 × 10-4 -1.62 × 10-3 ; dormant area 2.06 × 10-3 -1.01 × 10-2 and 2.09 × 10-4 -1.04 × 10-3 ; entrance 1.85 × 10-3 -9.09 × 10-3 and 1.87 × 10-4 -9.27 × 10-4 ; boundary 1.82 × 10-3 -8.82 × 10-3 and 2.09 × 10-4 -8.94 × 10-4 for P:I = 1:103 and 1:104 respectively, while the risk of respiratory infection risks were in the magnitude of 10-1 for all four locations. The estimated risk of workers developing respiratory and gastrointestinal infections were high for all activities assessed at the dumpsite.

A pilot randomised controlled trial of befriending by volunteers in people with intellectual disability and depressive symptoms.

BACKGROUND: People with intellectual disability (ID) are more likely to experience chronic depression compared with the general population, which may be compounded by loneliness and lower levels of social support. Befriending aims to provide social support and promote engagement in community activities. No randomised controlled trials have examined whether befriending improves symptoms of depression and social outcomes in people with ID. The aim of this pilot trial was to assess the feasibility and acceptability of a future larger trial of one-to-one befriending by volunteers in people with ID and depressive symptoms. METHODS: Participants were adults with mild or moderate ID with a score of 5 or more on the Glasgow Depression Scale for People with Learning Disabilities (GDS-LD). They were randomised to the intervention arm (matched to a volunteer befriender for 6 months) or the control arm (usual care). Volunteers received training and supervision provided by two community befriending schemes. The main outcomes were feasibility of recruitment (minimum target n = 35), retention rate of participants, adherence (minimum 10 meetings), acceptability of the intervention, changes in depressive symptoms (assessed at baseline and 6 months) and feasibility of collecting data for a health economic analysis. RESULTS: Recruitment was challenging, and only 16 participants with ID and 10 volunteers were recruited. Six participants were matched with a volunteer and no participants dropped out (except for two volunteers). Four participants completed 10 meetings (mean 11.8). Befriending was thought to be acceptable, but modifications were suggested. An exploratory analysis suggested that GDS-LD score was lower in the intervention group compared with the control group after adjusting for baseline scores, but not significant (adjusted mean difference: -4.0; 95% confidence interval: -11.2 to 3.2). CONCLUSIONS: A large trial would not be feasible based on the recruitment strategies employed in this study. A further feasibility study addressing these challenges or the use of other study designs should be considered.

A systematic review of studies describing the influence of informal social support on psychological wellbeing in people bereaved by sudden or violent causes of death.

BACKGROUND: Whilst any type of bereavement can be traumatic, bereavement through violent or sudden causes is associated with more severe negative health and wellbeing outcomes compared to other types of loss. Social support has been found to have a positive impact on wellbeing after traumatic events in general. However, this association appears to be less consistently demonstrated in studies that focus on bereavement, and the literature in this area has not yet been systematically reviewed. This study aimed to review the international literature to examine systematically whether there is an association between informal social support from family and friends after bereavement through sudden and/or violent causes and post-bereavement wellbeing. METHODS: We conducted a systematic search for quantitative studies that tested for an association between social support and any outcome related to wellbeing after a sudden and/or violent loss. Included studies were assessed for quality, and findings were reported using the approach of narrative synthesis. The review was pre-registered on Prospero (registration number CRD42018093704). RESULTS: We identified 16 papers that met inclusion criteria, 11 of which we assessed as being of good or fair quality and 5 as poor quality. Fifteen different wellbeing outcomes were measured across all studies. We found consistent evidence for an inverse association between social support and symptoms/presence of depression, predominantly consistent evidence for an inverse association between social support and symptoms/presence of post-traumatic stress disorder (PTSD), and conflicting evidence for an inverse association between social support and symptoms/presence of complicated grief. CONCLUSIONS: Our systematic review identified evidence to suggest that social support after sudden or violent bereavement is associated with a reduced severity of depressive and PTSD symptoms. Further longitudinal research is needed to explore potential causality in this relationship, widening the focus from common mental disorders to include other mental illnesses, wellbeing outcomes, and suicide-related outcomes after bereavement. There is also a need for consensus on the conceptualisation and measurement of social support. Our findings imply that interventions to improve access to and quality of social support may reduce the burden of mental illness after bereavement, and may therefore be worth investing in.

Molecular basis of dendritic atrophy and activity in stress susceptibility.

Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity. Overall, we identify NAc neuronal-subtype molecular control of dendritic morphology and related functional adaptations, which underlie susceptibility to stress.

Structure-activity relationship study of ProxyPhos chemosensors for the detection of proximal phosphorylation and other phosphate species.

Chemosensors for the detection of phosphate-containing biological species are in high need. Detection of proximally phosphorylated sites of PPi and those found in peptides and proteins has been demonstrated using chemosensors containing pyrene, as a fluorescent reporter, and a Zn2+-chelate, as a phosphate-binding group. Using these sensors, detection of proximal phosphate groups is afforded by binding of at least two of the sensor molecules to the adjacent phosphates, via the Zn2+ centres, leading to excimer formation between the pyrene groups and the corresponding shift in emission from 376 to 476 nm. Although several reports of this chemosensor class have been made, no detailed studies of selectivity of these sensors among major phosphate targets have been reported. In this study, a library of this class of chemosensors, termed ProxyPhos, which contained various linkers and Zn2+-chelating groups (i.e. DPA, cyclen and cyclam), was prepared and the effects of structural variation on the sensing efficiency and selectivity were evaluated among proximally phosphorylated peptides, proteins, nucleotides, Pi and PPi. As a result of this study, we have identified ProxyPhos library members that are most suitable for the detection of proximally phosphorylated peptides, PPi, UTP, and a DpYD peptide motif, and have generally provided a foundation for the selection of ProxyPhos chemosensors for further development of specific biologically relevant assays. The broad utility of ProxyPhos is further supported by the demonstrated lack of these sensors' cytotoxicity, ability to rapidly permeate into live and fixed cells and compatibility with gel staining methods.

The incidence of congenital syphilis in the United Kingdom: February 2010 to January 2015.

OBJECTIVE: To estimate the incidence of congenital syphilis in the UK. DESIGN: Prospective study. SETTING AND POPULATION: United Kingdom. METHODS: Children born between February 2010 and January 2015 with a suspected diagnosis of congenital syphilis were reported through an active surveillance system. MAIN OUTCOME MEASURES: Number of congenital syphilis cases and incidence. RESULTS: For all years, reported incidence was below the WHO threshold for elimination (<0.5/1000 live births). Seventeen cases (12 male, five female) were identified. About 50% of infants (8/17) were born preterm (<37 weeks' gestation): median birthweight 2000 g (865-3170 g). Clinical presentation varied from asymptomatic to acute disease, including severe anaemia, hepatosplenomegaly, rhinitis, thrombocytopaenia, skeletal damage, and neurosyphilis. One infant was deaf and blind. Median maternal age was 20 years (17-31) at delivery. Where maternal stage of infection was recorded, 6/10 had primary, 3/10 secondary and 1/10 early latent syphilis. Most mothers were white (13/16). Country of birth was recorded for 12 mothers: UK (n = 6), Eastern Europe (n = 3), Middle East (n = 1), and South East Asia (n = 2). The social circumstances of mothers varied and included drug use and sex work. Some experienced difficulty accessing health care. CONCLUSION: The incidence of congenital syphilis is controlled and monitored by healthcare services and related surveillance systems, and is now below the WHO elimination threshold. However, reducing the public health impact of this preventable disease in the UK is highly dependent on the successful implementation of WHO elimination standards across Europe. TWEETABLE ABSTRACT: Congenital syphilis incidence in the UK is at a very low level and well below the WHO elimination threshold.

Diversity and linkage disequilibrium in farmed Tasmanian Atlantic salmon.

Farmed Atlantic salmon (Salmo salar) is a globally important production species, including in Australia where breeding and selection has been in progress since the 1960s. The recent development of SNP genotyping platforms means genome-wide association and genomic prediction can now be implemented to speed genetic gain. As a precursor, this study collected genotypes at 218 132 SNPs in 777 fish from a Tasmanian breeding population to assess levels of genetic diversity, the strength of linkage disequilibrium (LD) and imputation accuracy. Genetic diversity in Tasmanian Atlantic salmon was lower than observed within European populations when compared using four diversity metrics. The distribution of allele frequencies also showed a clear difference, with the Tasmanian animals carrying an excess of low minor allele frequency variants. The strength of observed LD was high at short distances (<25 kb) and remained above background for marker pairs separated by large chromosomal distances (hundreds of kb), in sharp contrast to the European Atlantic salmon tested. Genotypes were used to evaluate the accuracy of imputation from low density (0.5 to 5 K) up to increased density SNP sets (78 K). This revealed high imputation accuracies (0.89-0.97), suggesting that the use of low density SNP sets will be a successful approach for genomic prediction in this population. The long-range LD, comparatively low genetic diversity and high imputation accuracy in Tasmanian salmon is consistent with known aspects of their population history, which involved a small founding population and an absence of subsequent introgression. The findings of this study represent an important first step towards the design of methods to apply genomics in this economically important population.

Effect of filter media thickness on the performance of sand drying beds used for faecal sludge management.

The effect of sand filter media thickness on the performance of faecal sludge (FS) drying beds was determined in terms of: dewatering time, contaminant load removal efficiency, solids generation rate, nutrient content and helminth eggs viability in the dried sludge. A mixture of ventilated improved pit latrine sludge and septage in the ratio 1:2 was dewatered using three pilot-scale sludge drying beds with sand media thicknesses of 150, 250 and 350 mm. Five dewatering cycles were conducted and monitored for each drying bed. Although the 150 mm filter had the shortest average dewatering time of 3.65 days followed by 250 mm and 350 mm filters with 3.83 and 4.02 days, respectively, there was no significant difference (p > 0.05) attributable to filter media thickness configurations. However, there was a significant difference for the percolate contaminant loads in the removal and recovery efficiency of suspended solids, total solids, total volatile solids, nitrogen species, total phosphorus, chemical oxygen demand, dissolved chemical oxygen demand and biochemical oxygen demand, with the highest removal efficiency for each parameter achieved by the 350 mm filter. There were also significant differences in the nutrient content (NPK) and helminth eggs viability of the solids generated by the tested filters. Filtering media configurations similar to 350 mm have the greatest potential for optimising nutrient recovery from FS.

The effect of nitrogen containing bisphosphonates, zoledronate and alendronate, on the production of pro-angiogenic factors by osteoblastic cells.

Bisphosphonates (BPs) have been shown to influence angiogenesis. This may contribute to BP-associated side-effects such as osteonecrosis of the jaw (ONJ) or atypical femoral fractures (AFF). The effect of BPs on the production of angiogenic factors by osteoblasts is unclear. The aims were to investigate the effect of (1) alendronate on circulating angiogenic factors; vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) in vivo and (2) zoledronate and alendronate on the production of VEGF and ANG-1 by osteoblasts in vitro. We studied 18 post-menopausal women with T score⩽-2 randomized to calcium/vitamin D only (control arm, n=8) or calcium/vitamin D and alendronate 70mg weekly (treatment arm, n=10). Circulating concentrations of VEGF and ANG-1 were measured at baseline, 3, 6 and 12months. Two human osteoblastic cell lines (MG-63 and HCC1) and a murine osteocytic cell line (MLO-Y4) were treated with zoledronate or alendronate at concentrations of 10(-12)-10(-6)M. VEGF and ANG-1 were measured in the cell culture supernatant. We observed a trend towards a decline in VEGF and ANG-1 at 6 and 12months following treatment with alendronate (p=0.08). Production of VEGF and ANG-1 by the MG-63 and HCC1 cells decreased significantly by 34-39% (p<0.01) following treatment with zoledronate (10(-9)-10(-6)M). Treatment of the MG-63 cells with alendronate (10(-7) and 10(-6)) led to a smaller decrease (25-28%) in VEGF (p<0.05). Zoledronate (10(-10)-10(-)(6)M) suppressed the production of ANG-1 by MG-63 cells with a decrease of 43-49% (p<0.01). Co-treatment with calcitriol (10(-8)M) partially reversed this zoledronate-induced inhibition. BPs suppress osteoblastic production of angiogenic factors. This may explain, in part, the pathogenesis of the BP-associated side-effects.

Self-sampling for community respiratory illness: a new tool for national virological surveillance.

This report aims to evaluate the usefulness of self-sampling as an approach for future national surveillance of emerging respiratory infections by comparing virological data from two parallel surveillance schemes in England. Nasal swabs were obtained via self-administered sampling from consenting adults (≥ 16 years-old) with influenza symptoms who had contacted the National Pandemic Flu Service (NPFS) health line during the 2009 influenza pandemic. Equivalent samples submitted by sentinel general practitioners participating in the national influenza surveillance scheme run jointly by the Royal College of General Practitioners (RCGP) and Health Protection Agency were also obtained. When comparable samples were analysed there was no significant difference in results obtained from self-sampling and clinician-led sampling schemes. These results demonstrate that self-sampling can be applied in a responsive and flexible manner, to supplement sentinel clinician-based sampling, to achieve a wide spread and geographically representative way of assessing community transmission of a known organism.

Preclinical assessment of a new magnetic resonance-based technique for determining bone quality by characterization of trabecular microarchitecture.

The utility of HR-CT to study longitudinal changes in bone microarchitecture is limited by subject radiation exposure. Although MR is not subject to this limitation, it is limited both by patient movement that occurs during prolonged scanning at distal sites, and by the signal-to-noise ratio that is achievable for high-resolution images in a reasonable scan time at proximal sites. Recently, a novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised one-dimensional magnetic resonance spatial frequency spectroscopy. PCT/US2012/068284 2012, James and Chase Magnetic field gradient structure characteristic assessment using one-dimensional (1D) spatial frequency distribution analysis. 7932720 B2, 2011) has been developed which provides both high-resolution and fast scan times, but which generates at a designated set of spatial positions (voxels) a one-dimensional signal of spatial frequencies. Appendix 1 provides a brief introduction to FSA. This article describes an initial exploration of FSA for the rapid, non-invasive characterization of trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from CT datasets and from CT-derived histomorphometry parameters, trabecular number (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). OVX caused a reduction of the higher frequency structures that correspond to a denser trabecular lattice, while increasing the preponderance of lower frequency structures, which correspond to a more open lattice. As one example measure, the centroid of the FSA spectrum (which we refer to as fSAcB) showed strong correlation in the same region with CT-derived histomorphometry values: Tb.Sp: r -0.63, p < 0.001; Tb.N: r 0.71, p < 0.001; BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5% reduction in fSAcB in OVX rats (p < 0.0001). In a longitudinal study, FSA showed that the age-related increase in higher frequency structures was abolished in OVX rats, being replaced with a 78-194% increase in lower frequency structures (2.4-2.8 objects/mm range), indicating a more sparse trabecular lattice (p < 0.05). The MR-based fine structure analysis enables high-resolution, radiation-free, rapid quantification of bone structures in one dimension (the specific point and direction being chosen by the clinician) of the spine.

A history of One Health.

One Health is not a new concept. It can be demonstrated that its origins and development literally run the gamut from A to Z, that is to say, from Aristotle to Zoobiquity. Indeed, the consequences of the interaction that occurs between ecosystems, animals and people have shaped, and continue to shape, the course of human events and history. A reasoned and evidence-based assessment of the history of One Health must first be founded on an agreed definition of the term, but, given the many disciplines and sciences involved, finding such a definition is no easy task. Furthermore, there is an extensive and growing list of visionary individuals who have, over the centuries, attempted to promote awareness and advance the conceptto improve the management of the risks and consequences that arise at the interface between animal, human and ecosystem health. The One Health ideas of the 21st Century constitute a re-conceptualisation of health management in response to the accelerating environmental changes of the past 100 years, changes that are associated with the parallel exponential growth and concentration of the global human population. Consequently, the concept of One Health must recognise the constantly evolving relationship between animals and humans and the planet they share.

Plasma ropivacaine concentrations during bilateral transversus abdominis plane infusions.

BACKGROUND: The transversus abdominis plane (TAP) block is a regional anaesthetic technique that blocks abdominal wall somatic afferent nerves. We conducted a prospective observational study to evaluate the venous plasma concentrations of ropivacaine during a continuous TAP infusion. METHODS: Twenty patients who were planned to undergo intra-abdominal cavity surgery requiring a mid-line laparotomy incision were enrolled. Patients were excluded if they had a history of chronic pain, opioid tolerance, renal or hepatic impairment, or contraindication to study medications. Subjects received a standardized general anaesthetic, and at the completion of surgery, ultrasound-guided subcostal or posterior TAP blocks and catheters. A TAP infusion of 2 mg ml(-1) ropivacaine was administered for 72 h after operation. Data collection during the 72 h included morphine requirements, pain scores, and plasma ropivacaine levels. RESULTS: TAP blocks and catheters were successfully inserted in all recruited subjects. The fourth subject experienced neurological symptoms attributed to local anaesthetic toxicity, but did not have high plasma ropivacaine concentrations. However, the protocol was amended for the subsequent 16 subjects, to a weight-based dosing regimen. The range of total plasma ropivacaine concentrations was 0.98-3.41 mg litre(-1) for posterior infusions and 0.96-3.48 mg litre(-1) for subcostal infusions. Four subjects had total ropivacaine levels >3.4 mg litre(-1). The range of unbound plasma ropivacaine concentrations was 0.022-0.135 mg litre(-1) for posterior infusions and 0.031-0.120 mg litre(-1) for subcostal infusions. CONCLUSION: Given the potential for high plasma concentrations from a bilateral TAP infusion technique, attention should be paid to individualized dosing strategies.