A Decision Guide for Assessing the Recently Extubated Patient's Readiness for Safe Oral Intake.

BACKGROUND: Postextubation dysphagia is a known consequence of endotracheal intubation. Several risk factors for postextubation dysphagia have been identified that could be used to help determine which patients should undergo swallowing assessment by an appropriate professional. LOCAL PROBLEM: At the authors' institution, critical care nurses, health care providers, and speech-language pathology professionals lacked a clear process for referring patients for swallowing assessment after extubation, resulting in inefficiency and confusion. Information to guide their decision-making in this area was needed. To address this need, a multidisciplinary group convened and developed a guide with specific indicators. METHODS: A review of the literature on postextubation dysphagia was conducted to determine the most appropriate indicators for the guide, which was piloted in the medical intensive care unit. The utilization rate was calculated. Referrals to speech-language pathology professionals were tabulated before and after the project. RESULTS: During the 11 months before implementation of the project, there were 994 speech-language pathology consultations for postextubation evaluation of swallowing. During the 11 months after implementation, there were 831 consultations, representing a 16.4% reduction. The decline in consultations resulted in cost savings in addition to preventing unnecessary testing before patients' resumption of oral intake. The utilization rate for the guide during the project was 58%. CONCLUSION: The decision guide was an effective tool to help nurses and health care providers determine which patients should be referred to speech-language pathology professionals for swallowing assessment after extubation, facilitating the appropriate use of limited health care resources.

Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Unobtrusive, Continuous LIDAR-Based Measurement of Gait Characteristics at Home.

This paper describes a novel approach to the unobtrusive assessment of a subset of gait characteristics using a light detection and ranging (LIDAR) device. The developed device is poised to enable unobtrusive, nearly continuous monitoring and inference of patients' gait characteristics to assess physical and cognitive states. The device provides a rapidly sampled signal representing the distance of a participant's body from the LIDAR device. The densely sampled distance estimation is processed by custom algorithms that can potentially be used to estimate various gait characteristics such as step size, cadence, double support, and even step-size symmetry.Clinical Relevance- Since gait is a complex behavior that requires seamless cooperation of multiple systems, including sensation, perception, muscular synergies, and even cognition. Subtle changes in gait may, therefore, indicate issues with physical and mental functionality. In addition to the walking speed, the gait monitoring results can provide inferences about the physical and cognitive states of the unobtrusively monitored individuals using their own data as a baseline.

National population prevalence of antibodies to SARS-CoV-2 in Scotland during the first and second waves of the COVID-19 pandemic.

OBJECTIVES: Studies that measure the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('seroprevalence') are essential to understand population exposure to SARS-CoV-2 among symptomatic and asymptomatic individuals. We aimed to measure seroprevalence in the Scottish population over the course of the COVID-19 pandemic - from before the first recorded case in Scotland through to the second pandemic wave. STUDY DESIGN: The study design of this study is serial cross sectional. METHODS: We tested 41,477 residual samples retrieved from primary and antenatal care settings across Scotland for SARS-CoV-2 antibodies over a 12-month period from December 2019-December 2020 (before rollout of COVID-19 vaccination). Five-weekly rolling seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Temporal trends in seroprevalence estimates and weekly SARS-CoV-2 notifications were compared. RESULTS: Five-weekly rolling seroprevalence rates were 0% until the end of March, when they increased contemporaneously with the first pandemic wave. Seroprevalence rates remained stable through the summer (range: 3%-5%) during a period of social restrictions, after which they increased concurrently with the second wave, reaching 9.6% (95% confidence interval [CI]: 8.4%-10.8%) in the week beginning 28th December in 2020. Seroprevalence rates were lower in rural vs. urban areas (adjusted odds ratio [AOR]: 0.70, 95% CI: 0.61-0.79) and among individuals aged 20-39 years and 60 years and older (AOR: 0.74, 95% CI: 0.64-0.86; AOR: 0.80, 95% CI: 0.69-0.91, respectively) relative to those aged 0-19 years. CONCLUSIONS: After two waves of the COVID-19 pandemic, less than one in ten individuals in the Scottish population had antibodies to SARS-CoV-2. Seroprevalence may underestimate the true population exposure as a result of waning antibodies among individuals who were infected early in the first wave.

Application of QMRA to prioritise water supplies for Cryptosporidium risk in New South Wales, Australia.

A Quantitative Microbial Risk Assessment (QMRA) framework was applied to assess 312 drinking water supply systems across regional New South Wales (NSW). The framework was needed to support the implementation of a recommendation in the Australian Drinking Water Guidelines (ADWG) for appropriate treatment barriers to be operating in systems 'at risk' for Cryptosporidium. The objective was to prioritise systems so that those with the highest risk could be identified and addressed first. The framework was developed in a pilot study of 30 systems, selected to represent the range of water supplies across regional NSW. From these, source water categories were defined to represent local conditions with reference to the literature and Cryptosporidium risk factors. Values for Cryptosporidium oocyst concentration were assigned to the categories to allow quantification of the health risk from those water sources. The framework was then used to assess the risks in all 312 regional drinking water supply systems. Combining the disciplined approach of QMRA with simple catchment and treatment information and categorical risk outputs provided a useful and transparent method for prioritising systems for further investigation and potential risk management intervention. The risk rankings for drinking water supplies from this QMRA process have been used to set priorities for a large State Government funding program.

Imaging radiation dose in breast radiotherapy by X-ray CT calibration of Cherenkov light.

Imaging Cherenkov emission during radiation therapy cancer treatments can provide a real-time, non-contact sampling of the entire dose field. The emitted Cherenkov signal generated is proportional to deposited dose, however, it is affected by attenuation from the intrinsic tissue optical properties of the patient, which in breast, ranges from primarily adipose to fibroglandular tissue. Patients being treated with whole-breast X-ray radiotherapy (n = 13) were imaged for 108 total fractions, to establish correction factors from the linear relationships between Cherenkov light and CT number (HU). This study elucidates this relationship in vivo, and a correction factor approach is used to scale each image to improve the linear correlation between Cherenkov emission intensity and dose ([Formula: see text]). This study provides a major step towards direct quantitative radiation dose imaging in humans by utilizing non-contact camera sensing of Cherenkov emission during the radiation therapy treatment.

Imaging Cherenkov photon emissions in radiotherapy with a Geiger-mode gated quanta image sensor.

The emission of Cherenkov photons from human and animal tissue can be observed during clinical x-ray or particle beam irradiation. However, imaging this weak emission with the necessary single-photon sensitivity in the clinical room is challenging because of milliwatt-level ambient room lighting and the presence of stray high-energy radiation. In this Letter, we demonstrate, to the best of our knowledge, the first Cherenkov imaging with a time-gated quanta image sensor employing a large single-photon avalanche diode (SPAD) array. Detecting single Cherenkov photons was possible with high photon avalanche gain, fast temporal gating, and moderately high ∼7% photon detection probability. Single-bit digitization and active SPAD quenching enabled stray x-ray noise suppression and photon-noise-limited imaging in a clinical environment. This type of imaging allows the knowledge of location, shape, and surface dose of the therapeutic beam radiotherapy with the stability of solid state-based detection.

Skeletal Muscle Oxygenation Measured by EPR Oximetry Using a Highly Sensitive Polymer-Encapsulated Paramagnetic Sensor.

We have incorporated LiNc-BuO, an oxygen-sensing paramagnetic material, in polydimethylsiloxane (PDMS), which is an oxygen-permeable, biocompatible, and stable polymer. We fabricated implantable and retrievable oxygen-sensing chips (40 % LiNc-BuO in PDMS) using a 20-G Teflon tubing to mold the chips into variable shapes and sizes for in vivo studies in rats. In vitro EPR measurements were used to test the chip's oxygen response. Oxygen induced linear and reproducible line broadening with increasing partial pressure (pO2). The oxygen response was similar to that of bare (unencapsulated) crystals and did not change significantly on sterilization by autoclaving. The chips were implanted in rat femoris muscle and EPR oximetry was performed repeatedly (weekly) for 12 weeks post-implantation. The measurements showed good reliability and reproducibility over the period of testing. These results demonstrated that the new formulation of OxyChip with 40 % LiNc-BuO will enable the applicability of EPR oximetry for long-term measurement of oxygen concentration in tissues and has the potential for clinical applications.

Case report of a near medical event in stereotactic radiotherapy due to improper units of measure from a treatment planning system.

PURPOSE: The authors hereby notify the Radiation Oncology community of a potentially lethal error due to improper implementation of linear units of measure in a treatment planning system. The authors report an incident in which a patient was nearly mistreated during a stereotactic radiotherapy procedure due to inappropriate reporting of stereotactic coordinates by the radiation therapy treatment planning system in units of centimeter rather than in millimeter. The authors suggest a method to detect such errors during treatment planning so they are caught and corrected prior to the patient positioning for treatment on the treatment machine. METHODS: Using pretreatment imaging, the authors found that stereotactic coordinates are reported with improper linear units by a treatment planning system. The authors have implemented a redundant, independent method of stereotactic coordinate calculation. RESULTS: Implementation of a double check of stereotactic coordinates via redundant, independent calculation is simple and accurate. Use of this technique will avoid any future error in stereotactic treatment coordinates due to improper linear units, transcription, or other similar errors. CONCLUSIONS: The authors recommend an independent double check of stereotactic treatment coordinates during the treatment planning process in order to avoid potential mistreatment of patients.

Suitability of an automated nucleic acid extractor (easyMAG) for use with hepatitis C virus and human immunodeficiency virus type 1 nucleic acid amplification testing.

Serological screening assays have greatly reduced, but not eliminated, the risk of transmission of viral infections by transfusion of blood and blood products. In addition, the 1999 regulation of the European Agency for the Evaluation of Medicinal Products requiring all plasma for fractionation to have tested negative for hepatitis C virus (HCV) RNA (CPMP/BWP/390/97, 1998) led many blood transfusion services to introduce nucleic acid amplification technology (NAT) to screen blood donations for HCV, and in some services for human immunodeficiency virus (HIV) and hepatitis B virus (HBV). BioMérieux's second-generation system, the NucliSENS easyMAG, was evaluated as a suitable platform for the automated extraction of nucleic acids for use with the existing SNBTS NAT assays. Two nucleic acid extraction protocols were examined, either lysis on the easyMAG (on board) or a 30-min pre-incubation of the sample with lysis buffer at 37 °C (off board). Off board lysis was found to extract nucleic acid more efficiently for both HCV and HIV NAT assays although the improvement was more marked with HIV. The 95% limit of detections (LODs) were 10.11 IU/ml (on board) and 7.21 IU/ml (off board) for HCV and 55.11 IU/ml (on board) and 34.13 (off board) for HIV. Using the more sensitive off board lysis, nucleic acid extraction specificity, robustness and reliability of the easyMAG were examined and over 10,000 Scottish blood donations (in 107 pools of 95 donations) were tested for HCV and HIV in parallel with the existing assay. The results indicate that the easyMAG is a suitable and flexible nucleic acid extraction system, providing high quality nucleic acids and a rapid response alternative to commercial, fully automated, approved blood screening platforms.

The Joint Theatre Clinical Case Conference (JTCCC): clinical governance in action.

OBJECTIVES: To quantify the type and nature of the lessons and issues arising from the Joint Theatre Clinical Case Conference METHODS: An evaluation of all JTCCC minutes from inception on 30 Mar 07 to 05 Jun 08 (n = 61) was performed in Jul 08. Each separate issue (n = 207) was assigned a NATO 'J' category and further sub-divided into clinical and non-clinical issues. Detail of whether the issues were raised for information only, or required action to be taken was recorded, as was the outcome of this action. RESULTS: A wide range of clinical and non-clinical issues (J1-J8), were identified. 23% (47) of the 207 issues were raised for information only. 77% (160) issues required action to be taken. 109 were dosed within 3 weeks. 23 took more than 3 weeks to close. Eight weeks after the study period 28 issues were still being actively resolved. 85% of JTCCC teleconferences had full participation from both theatres. Technical difficulties and/or the treatment of casualties prevented the participation of one or both theatres on 9 occasions. CONCLUSIONS: JTCCC supports deployed clinicians and enables rapid resolution of issues affecting combat casualty care. It is limited by its focus on UK casualties only. Although intended as a Clinical Governance tool the evidence of this review is that JTCCC has wider effects in a number of clinical and non-clinical areas.

Regulatory IL4+CD8+ T cells in patients with ankylosing spondylitis and healthy controls.

OBJECTIVES: Interleukin (IL)4+CD8+ regulatory T cells (Treg) obtained from peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) by coculture with autologous dendritic cells (DC) have been previously described. In the present work, the proportions of IL4+CD8+ T cells in PB from patients with AS and controls are examined; in addition the conditions required for the generation of IL4+CD8+ Treg cells and their frequency in T cell lines from patients with AS and controls are investigated. METHODS: CD8+ T cells were either stimulated non-specifically ex vivo and intracellular cytokines examined, or cocultured with DC and other stimuli, for 2 weeks. The resulting lines were analysed for cytokine expression. Clones derived from these lines were tested for regulatory function. RESULTS: PBMCs from patients with AS and from human leukocyte antigen (HLA)-B27+ healthy controls contained a higher frequency of IL4+CD8+ T cells than those from HLA-B27- controls. Likewise, CD8+ T cell lines obtained by coculture with DC contained a higher ratio of IL4+ to interferon (IFN)gamma+ cells when obtained from patients with AS or HLA-B27+ controls. T cell clones obtained from these lines showed regulatory activity. Outgrowth of IL4+ CD8+ T cells required contact with DC, but not maturation with lipopolysaccharide (LPS); allogeneic DC were also effective. Coculture with lymphoblastoid cells, or anti-CD3/CD28 microbeads, produced only expansion of IFN gamma-producing CD8+ T cells. CONCLUSIONS: The higher proportion of CD8+ cells which can produce IL4 in PB and in expanded CD8+ T cell lines suggests an altered pattern of CD8+ T cell differentiation in AS and in HLA-B27+ healthy individuals. This predisposition to generate IL4+CD8+ T cells may play a role in pathogenesis of spondyloarthritis.

Increased IL-4+ CD8+ T cells in peripheral blood and autoreactive CD8+ T cell lines of patients with inflammatory arthritis.

OBJECTIVE: To measure the frequencies of IL-4+ CD8+ T cells from patients with AS and RA, and to assess their clinical relevance and properties. METHODS: Peripheral blood (PB) and clinical data were obtained from 37 AS, 36 RA patients and 37 healthy controls. We also generated IL-4-producing CD8+ T cell lines and clones by co-culture with autologous dendritic cells. Using flow cytometry, we evaluated intracellular cytokine expression by T cells following stimulation with PMA and calcium ionophore. The phenotype and ability of the IL-4-producing CD8+ T cell clones to suppress IFN-gamma production were examined. RESULTS: The percentages of IL-4+ CD8+ T cells were higher in PB of patients with AS and RA than controls (medians 0.90 and 0.84% vs 0.30%). In RA, patients with active inflammation had an increased percentage of IL-4+ CD8+ T cells. Higher frequencies of IL-4+ CD8+ T cells were also found in CD8+ T cell lines established from patients with arthritis. Interestingly, most IL-4+ CD8+ T cells produced TNF-alpha. Cloning the CD8+ T cell lines yielded more IL-4-producing clones from AS (23%) and RA patients (14%) than from controls (7%). The ability to suppress IFN-gamma production was observed in 56% (AS) and 85% (RA) of IL-4-producing clones. Suppressive IL-4+ CD8+ T cell clones from RA patients showed a similar regulatory phenotype to the clones previously isolated from AS patients. CONCLUSIONS: Expansion of IL-4+ CD8+ T cells, which may include precursors of a regulatory CD8+ T cell subset, may represent a general response to chronic joint inflammation.

Food portion weights in primary and secondary school lunches in England.

BACKGROUND: National Nutritional Standards for school lunches were reintroduced in 2001, and included guidance on portion sizes for primary schools. For the first time since 1997, nationally representative data on school food portion sizes in England have been collected using direct assessment rather than reported portion sizes. METHODS: Food portions were weighed directly in foods served in nationally representative samples of primary and secondary school meals. Results were grouped by food or food group. RESULTS: The number of portions weighed was 7975 in primary schools and 3354 in secondary schools. Individual portion weights were grouped by food or food group to yield mean, median, SD and inter-quartile range. For a given food or food group, the number of portions weighed varied from 5 to 210 portions in primary schools and between 5 and 194 portions in secondary schools. CONCLUSIONS: The results provide a good representation of typical portion weights for different foods and food groups in primary and secondary schools in England. Portion size is one factor that determines nutrient intake. New standards for school lunches are both nutrient and food-based. Guidance on portion weights will help to ensure that pupils consume the correct balance of foods to obtain the recommended nutrient intake. The present findings complement and extend existing guidance on portion sizes for pupils in schools in England and Scotland.

Detection of HTLV-I and -II in Scottish blood donor samples and archive donations.

BACKGROUND AND OBJECTIVES: Positive samples identified during routine serological screening for HCV (hepatitis C virus), HBV (hepatitis B virus) and HIV (human immunodeficiency virus) are confirmed by nucleic acid testing in the SNBTS (Scottish National Blood Transfusion Service) PCR Reference laboratory. Serological screening for HTLV-I (human T-cell lymphotropic virus type I) and -II was implemented in Scotland in November 2002, at which time a PCR assay was not available for confirmation. Our aim was to develop a real-time PCR assay that could be used for the confirmation of samples showing HTLV-I serological positive or indeterminate reactivity and to investigate whether a serologically silent carrier status exists ('Tax' only) in the Scottish donor population. MATERIALS AND METHODS: A real-time HTLV PCR was devised using a lymphoblastoid cell line which has HTLV-I sequence integrated in the genome (C8166 cells). These were spiked into peripheral blood mononuclear cells. The assay was evaluated on archived serologically confirmed HTLV-positive samples and new positives identified since implementation of screening. RESULTS: HTLV-I and -II were detected in cells and plasma from stored donations and a serological positive donation identified in routine screening. HTLV DNA can also be amplified from the plasma obtained from plasma preparation tubes. There was no evidence of a carrier status ('Tax' only) in 100 serologically negative blood donors tested. The PCR assay developed is reliable and sensitive, capable of identifying one copy of HTLV-I. CONCLUSIONS: The HTLV PCR is a useful addition for HTLV confirmation, especially in serologically indeterminate samples and for look-back studies. HTLV PCR confirmation will provide additional useful information for donor medical staff for counselling donors.

Detection of HCV and HIV-1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. MATERIALS AND METHODS: When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. RESULTS: The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. CONCLUSION: The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.

Teleradiology: threat or opportunity?

The rapid advances in information technology and communication bandwidth have spawned an equally rapid development of clinical teleradiology. Current computer technology and communication capability allow easy transfer of diagnostic images, of any complexity, to any location in the world. This provides the opportunity to acquire swift primary and secondary diagnostic opinions from the remotest of locations, often at economically attractive rates, with the potential for easing the burden on hard-pressed departments of radiology. However, this comes at the potential cost of distancing the clinical radiologist from the patient, with consequent impact upon direct clinical care. As this technology advances across the world, it is vital that UK radiologists are familiar with the clinical implications, the medicolegal framework within which the field operates and the associated governance issues. This paper reviews current practice and discusses the associated risks.