Antimicrobial prophylaxis is not indicated for horses undergoing general anaesthesia for elective orthopaedic MRI.

BACKGROUND: Post-anaesthetic fever is a known complication of general anaesthesia, however, its incidence in horses undergoing elective magnetic resonance imaging (MRI) is unknown. OBJECTIVE: To determine the incidence of post-anaesthetic fever in horses undergoing elective orthopaedic MRI and determine whether prophylactic antimicrobial therapy would be associated with a reduction in the incidence of post-anaesthetic fever. We hypothesised that prophylactic antimicrobials would be associated with a reduction in the incidence of post-anaesthetic fever. STUDY DESIGN: Retrospective cross-sectional study. METHODS: This retrospective study included 791 elective orthopaedic MRIs in systemically healthy horses between June 2006 and March 2020 that recovered from general anaesthesia and did not undergo surgery or intensive medical therapy soon after recovery. Potential factors associated with post-anaesthetic fever were evaluated using multivariable logistic regression. Case signalment, travel time, preanaesthetic haematology and fibrinogen abnormalities, use of prophylactic antimicrobials, peri-anaesthetic nonsteroidal anti-inflammatories, anaesthesia time and recovery time were all evaluated for association with post-anaesthetic fever. RESULTS: Of 791 MRI cases, 44 (5.6%) developed a post-anaesthetic fever. Horses that received prophylactic antimicrobials were [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.98-7.46; p ≤ 0.001] more likely to develop a post-anaesthetic fever than those that did not receive antimicrobials. Young horses (1-4 years of age) were (OR 2.8, 95% CI 1.26-6.17; p = 0.01) more likely to develop fever compared with adult horses (≥5 years of age). MAIN LIMITATIONS: Limitations of this study pertain to retrospective analysis including nonrandomised case selection and incomplete data records. CONCLUSIONS: While fever may indicate infection, the majority of early post-anaesthetic fevers resolved before discharge from the hospital with no identified cause. The use of prophylactic antimicrobials to reduce the risk of post-anaesthetic fever for elective MRI is not supported by this study.

CONTEXTO: Febre é uma complicação comum após anestesia geral. Contudo, a incidência de febre em cavalos submetidos à ressonância magnética (RM) é desconhecida. OBJETIVO: Determinar a incidência de febre pós­anestésica em cavalos submetidos à RM devido à lesões ortopédicas e determinar se terapia antimicrobiana é necessária para reduzir a incidência de febre pós­anestésica. Nossa hipótese é que o uso de antimicrobianos é associado com a redução da incidência de febre pós­anestésica. DELINEAMENTO DO ESTUDO: Estudo retrospectivo transversal. METODOLOGIA: Esse estudo retrospectivo incluiu 791 equinos submetidos à RM por motivos ortopédicos, entre Junho de 2006 e Março de 2020, que recuperaram de anestesia geral, e não foram submetidos à cirurgia ou terapia intensa logo após a recuperação. Fatores que potencialmente poderiam ser associados com febre pós­anestésica foram avaliados utilizando regressão logística multivariada. Informações do paciente, como sexo e idade, tempo de viagem, anormalidades nos exames de sangue (hemograma e bioquímico) pré­anestésico, uso profilático de antimicrobianos, uso de anti­inflamatório não­esteroidal no período peri­anestésico, tempo de anestesia, e tempo de recuperação foram avaliados para possível associação com febre pós­anestésica. RESULTADOS: Dos 791 casos de RM, 44 (5.6%) desenvolveram febre pós­anestésica. Cavalos que receberam terapia antimicrobiana profilática foram (OR 3.8, 95% CI 1.98­7.46; p ≤ 0.001) vezes mais prováveis de desenvolverem febre pós­anestésica do que aqueles que não receberam antimicrobianos. Cavalos jovens (1­4 anos de idade) foram OR 2.8, 95% CI 1.26­6.17; p = 0.01) vezes mais prováveis de desenvolverem febre comparado com cavalos adultos (≥5 anos de idade). PRINCIPAIS LIMITAÇÕES: As limitações deste estudo são aquelas de uma análise retrospectiva, incluindo a seleção não randomizada dos pacientes e prontuários incompletos. CONCLUSÕES: Enquanto febre pode indicar a presença de infecção, a maioria das febres no período logo após anestesia se resolveram antes da alta do hospital e não tiveram nenhuma causa identificada. O uso profilático de antimicrobianos para reduzir a possível chance de febre pós­anestésica em casos de RM eletiva não é suportada por este estudo.

Feasibility and acceptability of using the Alarm Distress BaBy (ADBB) scale within universal health visiting practice in England: a mixed-methods study protocol.

INTRODUCTION: The Alarm Distress BaBy (ADBB) scale developed by Guedeney and Fermanian in 2001, is a validated screening tool designed for use by healthcare practitioners to identify infant social withdrawal. This study will explore the acceptability and feasibility of the use of the full ADBB scale and a modified ADBB (m-ADBB) scale as part of routine health visiting visits in England. METHODS AND ANALYSIS: A mixed methods sequential exploratory design will be used. Five health visitors will be trained in using the ADBB scale and 20 in the m-ADBB scale, from two National Health Service sites in England. Qualitative semi-structured interviews will be carried out with health visitors after they receive the training and again 2 months after using the scales in routine family health visits. Quantitative data will also be collected from the same participants for a range of items during the study period. The theoretical framework of Normalisation Process Theory will underpin the study, to provide in-depth explanations of the implementation process. Qualitative data will be analysed using thematic analysis. Quantitative data will be analysed using descriptive analysis. ETHICS AND DISSEMINATION: Ethical approval was granted by the University of Oxford Departmental Research Ethics Committee. Dissemination of results will be via organisational websites, social media platforms, newsletters, professional networks, conferences and journal articles.

Kinematics of the equine distal sesamoid (navicular) bone of the thoracic limb.

OBJECTIVE: To quantify the translation and angular rotation of the distal sesamoid bone (DSB) using computed tomography (CT) and medical modeling software. SAMPLE: 30 thoracic limbs from equine cadavers. PROCEDURES: Partial (n = 12), full (8), and matched full and subsequently transected (10) thoracic limbs were collected. Bone volume CT images were acquired in three positions: extension (200° metacarpophalangeal angle), neutral (180°), and maximal flexion (110°). Mean translation and angular rotation of each DSB were recorded. Differences were determined with two-way ANOVA and post hoc Tukey's tests for pairwise comparisons; P value was set at < 0.05. RESULTS: Dorsal translation was significant during extension (1.4 ± 0.4 mm full limbs and 1.3 ± 0.2 mm partial limbs, P < 0.001). Distal translation was significant during extension (1.9 ± 0.4 mm full and 1.1 ± 0.4 mm partial) and flexion (5.4 ± 0.7 mm full and 6.22 ± 0.6 mm partial, P < 0.001). Rotation was significant (P < 0.001) about the mediolateral axis during extension (17.1° ± 1.4°) and flexion (2.6° ± 1.3°). Translation and rotation of the DSB were significantly different (P < 0.001) between full and partial limbs. CLINICAL RELEVANCE: This study provides the first quantification of translation and angular rotation of the DSB within the equine hoof. Partial limbs had significantly reduced movement compared to full limbs, suggesting that transection of flexor tendons alters distal thoracic limb kinematics. Further studies are required to determine if pathologic changes in the podotrochlear apparatus have an impact in clinical lameness outcomes.

Three-dimensional printed surgical guides for keratoma removal in horses using computed tomography or magnetic resonance imaging-based segmentation.

OBJECTIVE: To report the technique, surgical approach, and postoperative features in horses treated via a 3-dimensional (3D) printed guide-assisted keratoma resection created using computed tomography (CT) or magnetic resonance imaging (MRI)-based segmentation. ANIMALS: Five client-owned horses. STUDY DESIGN: Short case series. METHODS: Horses were placed under general anesthesia for imaging (CT and MRI) and underwent a second anesthesia for surgery. Two horses had guides created from CT-based imaging, 3 horses had guides created from MRI. Various sized nonarbored hole saws were used to create accurate and precise portals for keratoma removal. Surgical sites were managed until keratinized granulation tissue had formed and the defect was sealed with an artificial hoof wall patch. RESULTS: All keratomas were successfully removed as a single piece either intact with the hoof wall or easily extracted after the hoof wall portal was created in a surgical time between 20 and 90 min. All CT created guides fitted without issue; MRI-created guides required minor adjustments with a rotary device for proper fit. All cases had minor debridement adjacent to P3 and circumferential lamellar tissue. All horses returned to previous level of performance 2 to 4 months postoperatively. CONCLUSION: Use of 3D printed guides led to accurate targeting of keratomas with small surgical portals and short surgical times. Due to challenges with MRI-based segmentation, CT is preferred.

Health visiting in England: The impact of the COVID-19 pandemic.

This focused review of evidence considers the impact of the pandemic in 2020 on families with children under 5 years in England, and the health visiting (HV) service that supports them. . Data were drawn from national surveys of health visitors (HVs) and parents, a freedom of information request of employers, published research, and national data. Framework analysis and triangulation, using the Key Elements of an effective HV service, were used to categorize the key findings. The findings from the review indicate that the impacts of the pandemic were wide-ranging and disproportionately affected the most disadvantaged families, increasing demand for HV support. HVs' ability to respond was compromised due to national policy decisions to partially stop the service and variations in local implementation including the redeployment of HVs, pre-existing workforce capacity issues, and the effectiveness of innovations to identify and support vulnerable families. The pandemic exacerbated factors that can lead to poorer outcomes for families. Key learning from the pandemic response, including the need to prioritize the HV service, must be acted upon to reduce ongoing impacts now and ensure that the service is equipped for future emergencies.

Three-dimensional printed guides for screw placement in equine navicular bones.

OBJECTIVE: To determine the influence of a custom 3D-printed guide for placement of cortical bone screws in the equine navicular bone. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Eight pairs of normal adult equine forelimbs. METHODS: A 3.5 × 55 mm cortical screw was placed in the longitudinal axis of each intact navicular bone. Screws were placed with a 3D-printed guide (3D) in one bone and with a traditional aiming device (AD) in the contralateral bone within each pair. Duration of surgery and the number of fluoroscopy images were compared between techniques. Screw placement was subjectively evaluated by gross examination and scored by three boarded veterinary surgeons. RESULTS: The use of a 3D-printed guide reduced the duration of surgery by 6.6 min (±1.5 min) compared to traditional screw placement (20.7 min ± 4.8 min, p < .01). Fewer peri-operative fluoroscopic images were obtained when the 3D guide was used (18 images ± 2.6 images vs. 40 images ± 5.1, p < .01). No difference was detected in navicular screw placement. CONCLUSION: The use of a 3D guide decreased the time required to place screws and the number of intraoperative images taken without affecting screw placement in intact navicular bones. CLINICAL RELEVANCE: 3D-printed guides can aid in the study, practice, and execution of surgical procedures reducing surgical time and radiation exposure throughout the operative period achieving similar results to those obtained with a conventional approach.

Use of Hausdorff Distance and Computer Modelling to Evaluate Virtual Surgical Plans with Three-Dimensional Printed Guides against Freehand Techniques for Navicular Bone Repair in Equine Orthopaedics.

OBJECTIVE: The aim of this study was to evaluate the surgical execution of a virtual surgical plan (VSP) with three-dimensional (3D) guides against a freehand approach in the equine navicular bone using an automated in silico computer analysis technique. STUDY DESIGN: Eight pairs of cadaveric forelimb specimens of adult horses were used in an ex vivo experimental study design with in silico modelling. Limbs received either a 3.5 mm cortical screw according to a VSP or using an aiming device. Using computed tomography and computer segmentation, a comparison was made between the executed screw and the planned screw using the Hausdorff distance (HD). RESULTS: Navicular bone mean HD registration error was -0.06 ± 0.29 mm. The VSP with 3D printing demonstrated significantly superior accuracy with a mean deviation of 1.19 ± 0.42 mm compared with aiming device group (3.53 ± 1.24 mm, p = 0.0018). The VSP group was 5.0 times more likely to result in a mean aberration of less than 1.0 mm (95% confidence interval, 0.62-33.4). A 3.5 mm screw with an optimal entry point can have a maximum deviation angle of 3.23 ± 0.07, 2.70 ± 0.06 and 2.37 ± 0.10 degrees in a proximal, dorsal and palmar direction respectively, prior to violating one of the cortical surfaces. CONCLUSION: Procedures performed using the 3D guides have a high degree of accuracy, with minimal mean deviations (<1 mm and <1 degree) of a VSP compared with those using the conventional aiming device. The use of VSP and the HD for evaluation of orthopaedic surgeries and outcome measures shows promise for simplifying and improving surgical accuracy.

Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer.

INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer. METHODS: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression. RESULTS: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute. CONCLUSIONS: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference.

Whole-body MRI compared with standard pathways for staging metastatic disease in lung and colorectal cancer: the Streamline diagnostic accuracy studies.

BACKGROUND: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer. OBJECTIVES: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C). DESIGN: The design was a prospective multicentre cohort study. SETTING: The setting was 16 NHS hospitals. PARTICIPANTS: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L). INTERVENTIONS: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography). REFERENCE STANDARD: Consensus panel decision using 12-month follow-up data. MAIN OUTCOME MEASURES: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness. RESULTS: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests. LIMITATIONS: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice. CONCLUSIONS: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 66. See the NIHR Journals Library website for further project information.

Colorectal and lung cancer are the leading causes of cancer-related deaths in the UK. Optimal treatment depends on accurately defining (or 'staging') the extent of disease, particularly if it has spread to other parts of the body such as the liver. Current staging pathways are complex and rely on a variety of tests that use X-rays, such as computed tomography and positron emission tomography­computed tomography scans. Patients often undergo multiple tests before starting treatment. Alternatively, it is possible to scan the whole body using magnetic resonance imaging without X-rays, and this may be more accurate and reduce the time and number of tests needed before treatment can start. We compared the ability to detect cancer spread, efficiency, patient experience and cost-effectiveness of staging based on whole-body magnetic resonance imaging with the standard NHS pathways in participants newly diagnosed with either lung (187 participants) or colorectal (299 participants) cancer. We found that the whole-body magnetic resonance imaging pathway was as accurate as standard staging pathways and resulted in very similar treatment decisions made by the clinical teams. The whole-body magnetic resonance imaging pathway detected 67% and 50% of participants with cancer spread in colorectal and lung cancer, respectively, compared with 63% and 54%, respectively, for standard staging. However, staging was quicker using whole-body magnetic resonance imaging (by 5 days for colorectal cancer and 6 days for lung cancer) and needed on average one less test to stage colorectal cancer. The whole-body magnetic resonance imaging pathway was also cheaper (costing on average £216 and £317 for colorectal and lung cancer, respectively, compared with £285 and £620, respectively, for standard pathways). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most preferred the whole-body magnetic resonance imaging pathway if it reduced the time to staging and/or the number of tests. Agreement between different radiology doctors interpreting the same whole-body magnetic resonance imaging scan was moderate for colon cancer and low for lung cancer, emphasising the need for training.

Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed colorectal cancer: the prospective Streamline C trial.

BACKGROUND: Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer. METHODS: The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete. FINDINGS: Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (-5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92-97]) and standard pathways (93% [90-96], p=0·48). Agreement with the multidisciplinary team's final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6-9]) than for the standard pathway (13 days [11-15]); a 5-day (3-7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211-221) for WB-MRI and £285 (260-310) for standard pathways. INTERPRETATION: WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost. FUNDING: UK National Institute for Health Research.

Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trial.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC. METHODS: The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete. FINDINGS: Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37-63) for WB-MRI and 54% (41-67) for standard pathways, a difference of 4% (-7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88-96]) and standard pathways (95% [91-98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12-14]) than for the standard pathway (19 days [17-21]); a 6-day (4-8) difference. The number of tests required was similar WB-MRI (one [1-1]) and standard pathways (one [1-2]). Mean per-patient costs were £317 (273-361) for WBI-MRI and £620 (574-666) for standard pathways. INTERPRETATION: WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs. FUNDING: UK National Institute for Health Research.

Patient preferences for whole-body MRI or conventional staging pathways in lung and colorectal cancer: a discrete choice experiment.

OBJECTIVES: To determine the importance placed by patients on attributes associated with whole-body MRI (WB-MRI) and standard cancer staging pathways and ascertain drivers of preference. METHODS: Patients recruited to two multi-centre diagnostic accuracy trials comparing WB-MRI with standard staging pathways in lung and colorectal cancer were invited to complete a discrete choice experiment (DCE), choosing between a series of alternate pathways in which 6 attributes (accuracy, time to diagnosis, scan duration, whole-body enclosure, radiation exposure, total scan number) were varied systematically. Data were analysed using a conditional logit regression model and marginal rates of substitution computed. The relative importance of each attribute and probabilities of choosing WB-MRI-based pathways were estimated. RESULTS: A total of 138 patients (mean age 65, 61% male, lung n = 72, colorectal n = 66) participated (May 2015 to September 2016). Lung cancer patients valued time to diagnosis most highly, followed by accuracy, radiation exposure, number of scans, and time in the scanner. Colorectal cancer patients valued accuracy most highly, followed by time to diagnosis, radiation exposure, and number of scans. Patients were willing to wait 0.29 (lung) and 0.45 (colorectal) weeks for a 1% increase in pathway accuracy. Patients preferred WB-MRI-based pathways (probability 0.64 [lung], 0.66 [colorectal]) if they were equivalent in accuracy, total scan number, and time to diagnosis compared with a standard staging pathway. CONCLUSIONS: Staging pathways based on first-line WB-MRI are preferred by the majority of patients if they at least match standard pathways for diagnostic accuracy, time to diagnosis, and total scan number. KEY POINTS: • WB-MRI staging pathways are preferred to standard pathways by the majority of patients provided they at least match standard staging pathways for accuracy, total scan number, and time to diagnosis. • For patients with lung cancer, time to diagnosis was the attribute valued most highly, followed by accuracy, radiation dose, number of additional scans, and time in a scanner. Preference for patients with colorectal cancer was similar. • Most (63%) patients were willing to trade attributes, such as faster diagnosis, for improvements in pathway accuracy and reduced radiation exposure.

Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model.

The authors are investigating self-complementary adeno-associated virus (scAAV) as a vector for intra-articular gene-delivery of interleukin-1 receptor antagonist (IL-1Ra), and its therapeutic capacity in the treatment of osteoarthritis (OA). To model gene transfer on a scale proportional to the human knee, a frequent site of OA incidence, studies were focused on the joints of the equine forelimb. Using AAV2.5 capsid and equine IL-1Ra as a homologous transgene, a functional ceiling dose of ∼5 × 1012 viral genomes was previously identified, which elevated the steady state levels of eqIL-1Ra in synovial fluids by >40-fold over endogenous production for at least 6 months. Here, using an osteochondral fragmentation model of early OA, the functional capacity of scAAV.IL-1Ra gene-delivery was examined in equine joints over a period of 12 weeks. In the disease model, transgenic eqIL-1Ra expression was several fold higher than seen previously in healthy joints, and correlated directly with the severity of joint pathology at the time of treatment. Despite wide variation in expression, the steady-state eqIL-1Ra in synovial fluids exceeded that of IL-1 by >400-fold in all animals, and a consistent treatment effect was observed. This included a 30-40% reduction in lameness and ∼25% improvement in total joint pathology by both magnetic resonance imaging and arthroscopic assessments, which included reduced joint effusion and synovitis, and improved repair of the osteochondral lesion. No vector-related increase in eqIL-1Ra levels in blood or urine was noted. Cumulatively, these studies in the equine model indicate scAAV.IL-1Ra administration is reasonably safe and capable of sustained therapeutic IL-1Ra production intra-articularly in joints of human scale. This profile supports consideration for human testing in OA.

Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.

Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produced eqIL-1Ra at levels 30- to 50-fold higher than the native sequence. The most efficient cDNA was packaged in AAV2.5 capsid, and following characterization in vitro, the virus was injected into the carpal and metacarpophalangeal joints of horses over a 100-fold dose range. A putative ceiling dose of 5 × 1012 viral genomes was identified that elevated the steady-state eqIL-1Ra in the synovial fluids of injected joints by >40-fold over endogenous levels and was sustained for at least 6 months. No adverse effects were seen, and eqIL-1Ra in serum and urine remained at background levels throughout. Using the 5 × 1012 viral genome dose of scAAV, and green fluorescent protein as a cytologic marker, the local and systemic distribution of vector and transduced cells following intra-articular injection scAAV.GFP were compared in healthy equine joints and in those with late-stage, naturally occurring OA. In both cases, 99.7% of the vector remained within the injected joint. Strikingly, the pathologies characteristic of OA (synovitis, osteophyte formation, and cartilage erosion) were associated with a substantial increase in transgenic expression relative to tissues in healthy joints. This was most notable in regions of articular cartilage with visible damage, where foci of brilliantly fluorescent chondrocytes were observed. Overall, these data suggest that AAV-mediated gene transfer can provide relatively safe, sustained protein drug delivery to joints of human proportions.

Perceived patient burden and acceptability of whole body MRI for staging lung and colorectal cancer; comparison with standard staging investigations.

OBJECTIVE: To evaluate perceived patient burden and acceptability of whole body MRI (WB-MRI) compared to standard staging investigations, and identify predictors of reduced tolerance. METHODS: Patients recruited to multicentre trials comparing WB-MRI with standard staging scans for lung and colorectal cancer were invited to complete two questionnaires: a baseline questionnaire at recruitment, measuring demographics, comorbidities, and distress; and a follow-up questionnaire after staging, measuring recovery time, comparative acceptability/satisfaction between WB-MRI and CT (colorectal cancer) and PET-CT (lung cancer), and perceived scan burden (scored 1, low; 7, high).  Results: 115 patients (median age 66.3 years; 67 males) completed follow up and 103 baseline questionnaires. 69 (63.9%) reported "immediate" recovery from WB-MRI and 73 (65.2%) judged it "very acceptable". Perceived WB-MRI burden was greater than for CT (p < 0.001) and PET-CT (p < 0.001). High distress and comorbidities were associated with greater WB-MRI burden in adjusted analyses, with deprivation only approaching significance (adjusted regression ß = 0.223, p = 0.025; ß = 0.191, p = 0.048; ß = -0.186, p = 0.059 respectively). Age (p = 0.535), gender (p = 0.389), ethnicity (p = 0.081) and cancer type (p = 0.201) were not predictive of WB-MRI burden. CONCLUSION:  WB-MRI is marginally less acceptable and more burdensome than standard scans, particularly for patients with pre-existing distress and comorbidities.  Advances in knowledge: This research shows that WB-MRI scan burden, although low, is higher than for current staging modalities among patients with suspected colorectal or lung cancer. Psychological and physical comorbidities adversely impact on patient experience of WB-MRI. Patients with high distress or comorbid illness may need additional support to undergo a WB-MRI.

Patient experience and perceived acceptability of whole-body magnetic resonance imaging for staging colorectal and lung cancer compared with current staging scans: a qualitative study.

OBJECTIVE: To describe the experience and acceptability of whole-body magnetic resonance imaging (WB-MRI) staging compared with standard scans among patients with highly suspected or known colorectal or lung cancer. DESIGN: Qualitative study using one-to-one interviews with thematic analysis. SETTING: Patients recruited from 10 hospitals in London, East and South East England between March 2013 and July 2014. PARTICIPANTS: 51 patients (31 male, age range 40-89 years), with varying levels of social deprivation, were recruited consecutively from two parallel clinical trials comparing the diagnostic accuracy and cost-effectiveness of WB-MRI with standard scans for staging colorectal and lung cancer ('Streamline-C' and 'Streamline-L'). WB-MRI was offered as an additional scan as part of the trials. RESULTS: In general WB-MRI presented a greater challenge than standard scans, although all but four patients completed the WB-MRI. Key challenges were enclosed space, noise and scan duration; reduced patient tolerance was associated with claustrophobia, pulmonary symptoms and existing comorbidities. Coping strategies facilitated scan tolerance and were grouped into (1) those intended to help with physical and emotional challenges, and (2) those focused on motivation to complete the scan, for example focusing on health benefit. Our study suggests that good staff communication could reduce anxiety and boost coping strategies. CONCLUSIONS: Although WB-MRI was perceived as more challenging than standard scans, it was sufficiently acceptable and tolerated by most patients to potentially replace them if appropriate. TRIAL REGISTRATION NUMBER: ISRCTN43958015 and ISRCTN50436483.

Effect of lidocaine on inflammation in equine jejunum subjected to manipulation only and remote to intestinal segments subjected to ischemia.

OBJECTIVE To examine effects of continuous rate infusion of lidocaine on transmural neutrophil infiltration in equine intestine subjected to manipulation only and remote to ischemic intestine. ANIMALS 14 healthy horses. PROCEDURES Ventral midline celiotomy was performed (time 0). Mild ischemia was induced in segments of jejunum and large colon. A 1-m segment of jejunum was manipulated by massaging the jejunal wall 10 times. Horses received lidocaine (n = 7) or saline (0.9% NaCl) solution (7) throughout anesthesia. Biopsy specimens were collected and used to assess tissue injury, neutrophil influx, cyclooxygenase expression, and hypoxia-inducible factor 1α (HIF-1α) expression at 0, 1, and 4 hours after manipulation and ischemia. Transepithelial resistance (TER) and mannitol flux were measured by use of Ussing chambers. RESULTS Lidocaine did not consistently decrease neutrophil infiltration in ischemic, manipulated, or control tissues at 4 hours. Lidocaine significantly reduced circular muscle and overall scores for cyclooxygenase-2 expression in manipulated tissues. Manipulated tissues had significantly less HIF-1α expression at 4 hours than did control tissues. Mucosa from manipulated and control segments obtained at 4 hours had lower TER and greater mannitol flux than did control tissues at 0 hours. Lidocaine did not significantly decrease calprotectin expression. Severity of neutrophil infiltration was similar in control, ischemic, and manipulated tissues at 4 hours. CONCLUSIONS AND CLINICAL RELEVANCE Manipulated jejunum did not have a significantly greater increase in neutrophil infiltration, compared with 4-hour control (nonmanipulated) jejunum remote to sites of manipulation, ischemia, and reperfusion. Lidocaine did not consistently reduce neutrophil infiltration in jejunum.

Response to early repeat celiotomy in horses after a surgical treatment of jejunal strangulation.

OBJECTIVE: To determine the outcome after early repeat celiotomy in horses operated for jejunal strangulation. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 22) that underwent repeat celiotomy for postoperative reflux (POR) and/or postoperative colic (POC) that did not improve within 48 hours from onset after initial surgical treatment of strangulating jejunal lesions by jejunojejunostomy (n = 14) or no resection (n = 8). METHODS: Medical records were reviewed for clinical signs, duration of signs before repeat surgery, surgical findings and treatment, and outcome. Survival was documented by phone call at long-term follow-up. The influence of POC and POR on timing of surgery were analyzed. Long-term survival was examined by Kaplan-Meier analyses. RESULTS: Repeat celiotomy was performed at a median of 57 hours after initial surgery and 16.5 hours from onset of signs, and earlier in horses with POC compared with POR (P < .05). A total of 3/22 horses were euthanatized under anesthesia. A total of 9 of 11 horses with initial jejunojejunostomy required resection of the original anastomosis due to anastomotic complications. In 8 horses without resection, second surgery included resection (4) or decompression (4). Repeat celiotomy was successful in 13/16 horses with POR. Repeat celiotomy eliminated POC in all horses (n = 9). A total of 19 horses were recovered from anesthesia and all survived to discharge. Incisional infections were diagnosed in 13/17 horses where both surgeries were performed through the same ventral median approach, and hernias developed in 4/13 infected incisions. Median survival time was 90 months. CONCLUSION: Repeat celiotomy can eliminate signs of POR and/or POC, and the additional surgery does not appear to aggravate POR. Criteria for repeat celiotomy in this study could provide guidelines for managing POC and POR after surgery for jejunal strangulation.

Streamlining staging of lung and colorectal cancer with whole body MRI; study protocols for two multicentre, non-randomised, single-arm, prospective diagnostic accuracy studies (Streamline C and Streamline L).

BACKGROUND AND AIMS: Rapid and accurate cancer staging following diagnosis underpins patient management, in particular the identification of distant metastatic disease. Current staging guidelines recommend sequential deployment of various imaging platforms such as computerised tomography (CT) and positron emission tomography (PET) which can be time and resource intensive and onerous for patients. Recent studies demonstrate that whole body magnetic resonance Imaging (WB-MRI) may stage cancer efficiently in a single visit, with potentially greater accuracy than current staging investigations. The Streamline trials aim to evaluate whether WB-MRI increases per patient detection of metastases in non-small cell lung and colorectal cancer compared to standard staging pathways. METHODS: The Streamline trials are multicentre, non-randomised, single-arm, prospective diagnostic accuracy studies with a novel design to capture patient management decisions during staging pathways. The two trials recruit adult patients with proven or highly suspected new diagnosis of primary colorectal (Streamline C) or non-small cell lung cancer (Streamline L) referred for staging. Patients undergo WB-MRI in addition to standard staging investigations. Strict blinding protocols are enforced for those interpreting the imaging. A first major treatment decision is made by the multi-disciplinary team prior to WB-MRI revelation based on standard staging investigations only, then based on the WB-MRI and any additional tests precipitated by WB-MRI, and finally based on all available test results. The reference standard is derived by a multidisciplinary consensus panel who assess 12 months of follow-up data to adjudicate on the TNM stage at diagnosis. Health psychology assessment of patients' experiences of the cancer staging pathway will be undertaken via interviews and questionnaires. A cost (effectiveness) analysis of WB-MRI compared to standard staging pathways will be performed. DISCUSSION: We describe a novel approach to radiologist and clinician blinding to ascertain the 'true' diagnostic accuracy of differing imaging pathways and discuss our approach to assessing the impact of WB-MRI on clinical decision making in real-time. The Streamline trials will compare WB-MRI and standard imaging pathways in the same patients, thereby informing the most accurate and efficient approach to staging. TRIAL REGISTRATION: Streamline C ISRCTN43958015 (registered 25/7/2012). Streamline L ISRCTN50436483 (registered 31/7/2012).