Diagnostic accuracy of the Abbott ID NOW SARS-CoV-2 rapid test for the triage of acute medical admissions.

BACKGROUND: Decisions to isolate patients at risk of having coronavirus disease 2019 (COVID-19) in the emergency department (ED) must be rapid and accurate to ensure prompt treatment and maintain patient flow whilst minimising nosocomial spread. Reverse transcription polymerase chain reaction (RT-PCR) assays are too slow to achieve this, and near-patient testing is being used increasingly to facilitate triage. The ID NOW severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) assay is an isothermal nucleic acid amplification near-patient test which targets the RNA-dependent RNA-polymerase gene. AIM: To assess the diagnostic performance of ID NOW as a COVID-19 triage tool for medical admissions from the ED of a large acute hospital. METHODS: All adult acute medical admissions from the ED between 31st March and 31st July 2021 with valid ID NOW and RT-PCR results were included. The diagnostic accuracy of ID NOW [sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)] was calculated against the laboratory reference standard. Discrepant results were explored further using cycle threshold values and clinical data. FINDINGS: Two percent (124/6050) of medical admissions were SARS-CoV-2 positive on RT-PCR. Compared with PCR, ID NOW had sensitivity and specificity of 83.1% [95% confidence interval (CI) 75.4-88.7] and 99.5% (95% CI 99.3-99.6), respectively. PPV and NPV were 76.9% (95% CI 69.0-83.2) and 99.6% (95% CI 99.5-99.8), respectively. The median time from arrival in the ED to ID NOW result was 59 min. CONCLUSION: ID NOW provides a rapid and reliable adjunct for the safe triage of patients with COVID-19, and can work effectively when integrated into an ED triage algorithm.

Injected human umbilical cord-derived mesenchymal stromal cells do not appear to elicit an inflammatory response in a murine model of osteoarthritis.

OBJECTIVE: This study investigated the effect of hUC-MSCs on osteoarthritis (OA) progression in a xenogeneic model. DESIGN: Male, 10 week-old C57BL/6 mice underwent sham surgery (n = 15) or partial medial meniscectomy (PMM; n = 76). 5x105 hUC-MSCs (from 3 donors: D1, D2 and D3) were phenotyped via RT-qPCR and immunoprofiling their response to inflammatory stimuli.They were injected into the mouse joints 3 and 6 weeks post-surgery, harvesting joints at 8 and 12 weeks post-surgery, respectively. A no cell 'control' group was also used (n = 29). All knee joints were assessed via micro-computed tomography (µCT) and histology and 10 plasma markers were analysed at 12 weeks. RESULTS: PMM resulted in cartilage loss and osteophyte formation resembling human OA at both time-points. Injection of one donor's hUC-MSCs into the joint significantly reduced the loss of joint space at 12 weeks post-operatively compared with the PMM control.This 'effective' population of MSCs up-regulated the genes, IDO and TSG6, when stimulated with inflammatory cytokines, more than those from the other two donors.No evidence of an inflammatory response to the injected cells in any animals, either histologically or with plasma biomarkers, arose. CONCLUSION: Beneficial change in a PMM joint was seen with only one hUC-MSC population, perhaps indicating that cell therapy is not appropriate for severely osteoarthritic joints. However, none of the implanted cells appeared to elicit an inflammatory response at the time-points studied. The variability of UC donors suggests some populations may be more therapeutic than others and donor characterisation is essential in developing allogeneic cell therapies.

Differences in plasma and peritoneal fluid proteomes identifies potential biomarkers associated with survival following strangulating small intestinal disease.

BACKGROUND: Strangulating small intestinal disease (SSID) carries a poor prognosis for survival in comparison to other types of colic, particularly if resection is required. Identification of markers which aid early diagnosis may prevent the need for resection, assist with more accurate prognostication and/or support the decision on whether surgical intervention is likely to be successful, would be of significant welfare benefit. OBJECTIVES: To apply an unbiased methodology to investigate the plasma and peritoneal fluid proteomes in horses diagnosed with SSID requiring resection, to identify novel biomarkers which may be of diagnostic or prognostic value. STUDY DESIGN: Prospective clinical study. METHODS: Plasma and peritoneal fluid from horses presented with acute abdominal signs consistent with SSID was collected at initial clinical examination. Samples from eight horses diagnosed with SSID at surgery in which resection of affected bowel was performed and four control horses subjected to euthanasia for orthopaedic conditions were submitted for liquid chromatography tandem mass spectrometry. Protein expression profiles were determined using label-free quantification. Data were analysed using analysis of variance to identify differentially expressed proteins between control and all SSID horses and SSID horses which survived to hospital discharge and those which did not. Significance was assumed at P≤0.05. RESULTS: A greater number of proteins were identified in peritoneal fluid than plasma of both SSID cases and controls, with 123 peritoneal fluid and 13 plasma proteins significantly differentially expressed (DE) between cases and controls (P<0.05, ≥2 fold change). Twelve peritoneal fluid proteins (P<0.036) and four plasma proteins (P<0.05) were significantly DE between SSID horses which survived and those which did not. MAIN LIMITATIONS: A low number of samples were analysed, there was variation in duration and severity of SSID and only short-term outcome was considered. CONCLUSIONS: Changes in peritoneal fluid proteome may provide a sensitive indicator of small intestinal strangulation and provide biomarkers relevant to prognosis.

Posterior capsular release is a biomechanically safe procedure to perform in total knee arthroplasty.

PURPOSE: Surgeons may attempt to strip the posterior capsule from its femoral attachment to overcome flexion contracture in total knee arthroplasty (TKA); however, it is unclear if this impacts anterior-posterior (AP) laxity of the implanted knee. The aim of the study was to investigate the effect of posterior capsular release on AP laxity in TKA, and compare this to the restraint from the posterior cruciate ligament (PCL). METHODS: Eight cadaveric knees were mounted in a six degree of freedom testing rig and tested at 0°, 30°, 60° and 90° flexion with ± 150 N AP force, with and without a 710 N axial compressive load. After the native knee was tested, a deep dished cruciate-retaining TKA was implanted and the tests were repeated. The PCL was then cut, followed by releasing the posterior capsule using a curved osteotome. RESULTS: With 0 N axial load applied, cutting the PCL as well as releasing the posterior capsule significantly increased posterior laxity compared to the native knee at all flexion angles, and CR TKA states at 30°, 60° and 90° (p < 0.05). However, no significant increase in laxity was found between cutting the PCL and subsequent PostCap release (n.s.). In anterior drawer, there was a significant increase of 1.4 mm between cutting the PCL and PostCap release at 0°, but not at any other flexion angles (p = 0.021). When a 710 N axial load was applied, there was no significant difference in anterior or posterior translation across the different knee states (n.s.). CONCLUSIONS: Posterior capsular release only caused a small change in AP laxity compared to cutting the PCL and, therefore, may not be considered detrimental to overall AP stability if performed during TKA surgery. LEVEL OF EVIDENCE: Controlled laboratory study.

An NIHR-approved two-year observational study on magnetically controlled growth rods in the treatment of early onset scoliosis.

Aims: The primary aim of this study was to evaluate the performance and safety of magnetically controlled growth rods in the treatment of early onset scoliosis. Secondary aims were to evaluate the clinical outcome, the rate of further surgery, the rate of complications, and the durability of correction. Patients and Methods: We undertook an observational prospective cohort study of children with early onset scoliosis, who were recruited over a one-year period and followed up for a minimum of two years. Magnetically controlled rods were introduced in a standardized manner with distractions performed three-monthly thereafter. Adverse events which were both related and unrelated to the device were recorded. Ten children, for whom relevant key data points (such as demographic information, growth parameters, Cobb angles, and functional outcomes) were available, were recruited and followed up over the period of the study. There were five boys and five girls. Their mean age was 6.2 years (2.5 to 10). Results: The mean coronal Cobb angle improved from 57.6° (40° to 81°) preoperatively, 32.8° (28° to 46°) postoperatively, and 41° (19° to 57°) at two years. Five children had an adverse event, with four requiring return to theatre, but none were related to the device. There were no neurological complications or infections. No devices failed. One child developed a proximal junctional kyphosis. The mean gain in spinal column height from T1 to S1 was 45.4 mm (24 to 81) over the period of the study. Conclusion: Magnetically controlled growth rods provide an alternative solution to traditional growing rods in the surgical management of children with early onset scoliosis, supporting growth of the spine while controlling curve progression. Their use has clear psychosocial and economic benefits, with the reduction of the need for repeat surgery as required with traditional growing rods. Cite this article: Bone Joint J 2018;100-B:507-15.

A test of the universal applicability of a commonly used principle of hoof balance.

This study used a UK trimming protocol to determine whether hoof balance is achieved (as defined by equivalence of geometric proportions) in cadaver limbs (n = 49) and two cohorts of horses (shod, n = 6, and unshod, n = 20; three trimming cycles). To determine equivalence, dorsal hoof wall length (DHWL), distance from the heel buttress to the centre of pressure (HBUT-COP) and distance from dorsal toe to centre of rotation (DT-COR) were calculated as a proportion of bearing border length (BBL) using digital photography. Geometric proportions were tested using Fieller's test of equivalence with limits of difference of 2.8%. In 22 cadaver limbs the location of external COR and COP was also mapped radiographically to the extensor process of the third phalanx and the centre of rotation of the distal interphalangeal joint. Equivalence of geometric proportions was not present following trimming in cadaver limbs or in the two cohorts. Although the dorsal hoof wall to heel wall ratio improved in cadaver and unshod horses after trimming, dorsal hoof wall and lateral heel parallelism was absent in all groups and COP was not consistently in line with the extensor process. Increased COP-COR distance occurred in shod horses and may relate to solar arch flattening. Palmar heel migration, however, occurred more in unshod horses. The study shows that equivalence of geometric proportions as a measure of static hoof balance was not commonly present and widely published measures and ratios of hoof balance rarely occurred in this sample population of horses.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

REASONS FOR PERFORMING STUDY: Colic remains a life-threatening condition in the horse. Ischaemia and reperfusion following correction of small intestinal strangulation may produce oxidative stress. The ability to withstand oxidative stress depends on antioxidant levels and may be linked to horse survival. OBJECTIVES: To measure peripheral antioxidant levels in horses undergoing exploratory laparotomy with small intestinal strangulation. STUDY DESIGN: Case-control study. METHODS: Blood and plasma were collected from horses undergoing exploratory laparotomy for small intestinal strangulation and stored at -80°C. Controls involved non-colic horses. Total plasma glutathione was measured spectrophotometrically at 412 nm using the 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB, Ellman's reagent) reaction. Samples containing scavenger (to remove reduced glutathione, GSH) were used to measure oxidised glutathione (GSSG). Glutathione reductase (GR) activity (u/l) was measured as the rate of GSH production at 412 nm. Glutathione peroxidise (GPx) activity (u/l) was measured as the change in optical density (340 nm) following the consumption of NADPH after GSSG production. All assays were purchased from BioAssay Systems (Hayward, California). Clinical data including arterial blood gas analysis were collected on admission. RESULTS: Glutathione reductase activity in horses with strangulating small intestinal lesions was significantly reduced compared to control horses (12.2 ± 1.1 u/l vs. 15.9 ± 0.8 u/l, P = 0.03, n = 6) whereas GPx activity did not significantly differ between colic and control horses (155.7 ± 48.7 u/l vs. 167.3 ± 30.1 u/l, P = 0.84, n = 6). Total glutathione, reduced or oxidised glutathione did not differ significantly between control and colic horses. A positive correlation existed between GR activity and Ca(2+) (r = 0.93) and K(+) (r = 0.75) whereas a strong negative correlation was present between GR activity and HCO3 (-) (r = -0.92) and PaCO2 (r = -0.96). CONCLUSIONS: Reduced plasma glutathione reductase activity with small intestinal strangulation indicates oxidative stress and may be related to systemic electrolyte/bicarbonate abnormalities. Ethical animal research: Study approval No. VREC219a. Explicit owner informed consent for inclusion of animals in this study was not stated. SOURCE OF FUNDING: Supported by the School of Veterinary Sciences, University of Liverpool. Competing interests: None declared.

Is anaesthesia of the deep branch of the lateral plantar nerve specific for the diagnosis of proximal metatarsal pain in the horse?

OBJECTIVES: To investigate the specificity of anaesthesia of the deep branch of the lateral plantar nerve (DB-LPN). METHODS: Twenty horses had DB-LPN anaesthesia performed by a single injection technique as part of a lameness investigation. The mechanical nociceptive threshold (NT) was measured using a handheld force meter at six points on the lateral aspect of the limb: before diagnostic anaesthesia (T0), and at 15 (T15) and 30 (T30) minutes post anaesthesia. Paired t-tests were performed and significance was set at p <0.05. In addition, ten cadaveric limbs were injected with 2.5 ml new methylene blue solution using a single injection technique to evaluate the extent of dye diffusion within the proximal metatarsal region. RESULTS: Compared with T0, there was a significant decrease in NT for all points combined at T15 (p = 0.008) and also at T30 (p = 0.007). There was a significant decrease in NT at T15 on the lateral third metatarsal bone (p = 0.012). At T30 there was a significant decrease in NT at the lateral sesamoid (p = 0.007), lateral third metatarsal bone (p = 0.031), and mid metatarsus (p = 0.033). Four out of 20 horses had a NT greater than 10 N at the lateral heel bulb at T30. In the cadaveric limbs, the total diffusion distance for all limbs (mean ± SD) was 70.4 ± 20.5 mm. Dye surrounded the DB-LPN in all limbs and the lateral plantar nerve (LPN) in nine out of 10 limbs. CLINICAL SIGNIFICANCE: Concurrent anaesthesia of the LPN is likely to occur when DB-LPN anaesthesia is performed using a single injection technique.

Factors associated with survival to hospital discharge following endoscopic treatment for synovial sepsis in 214 horses.

REASONS FOR PERFORMING STUDY: To determine risk factors involved in survival to hospital discharge of cases of synovial sepsis. OBJECTIVES: Investigate pre-, intra- and post operative factors involved in short-term survival of horses undergoing endoscopic treatment for synovial sepsis. STUDY DESIGN: Retrospective case series. METHODS: Clinical data were obtained for horses (>6 months old) undergoing endoscopic surgery as part of management for synovial sepsis over a 7-year period in a single hospital population. Descriptive data were generated for pre-, intra- and post operative variables. Multivariable logistic regression analysis was used to develop 3 models related to presurgical, surgical and post surgical stages of management with outcome defined as survival to hospital discharge. RESULTS: Two hundred and fourteen horses were included. In Model 1 (preoperative variables), increased preoperative synovial fluid total protein (TP) was associated with nonsurvival (OR 0.88, 95% CI 0.83-0.94, P<0.001) whereas the presence of a wound on admission was associated with survival (OR 4.75, 95% CI 1.21-18.65, P = 0.02). Model 2 (intraoperative variables) revealed that factors associated with decreased survival were anaesthetic induction outside of normal working hours (OR 0.36, 95% CI 0.15-0.88 P = 0.02) and presence of moderate/severe synovial inflammation at surgery (OR 0.28, 95% CI 0.12-0.67, P = 0.004). Model 3 (post operative variables) showed that increased post operative synovial fluid TP (OR 0.94, 95% CI 0.90-0.98, P = 0.013) and undertaking more than one endoscopic surgery for treatment (OR 0.19, 95% CI 0.05-0.70, P = 0.005) were associated with nonsurvival. Cut-off values for predicting survival were 55-60 g/l for preoperative and 50-55 g/l for post operative TP measurements. CONCLUSIONS: This study has identified factors associated with altered likelihood of survival to hospital discharge following endoscopic surgery for synovial sepsis. Prognosis for survival to hospital discharge can be based on evidence from this study at the key stages of management of horses with synovial sepsis.

Outcome of horses with synovial structure involvement following solar foot penetrations in four UK veterinary hospitals: 95 cases.

REASONS FOR PERFORMING STUDY: The factors associated with outcome following solar foot penetration involving synovial structures treated using endoscopic lavage have not been described in the UK population. OBJECTIVES: To provide descriptive data on horses with synovial contamination or sepsis following solar penetration in 4 UK equine referral hospitals and to identify specific factors associated with the outcome. STUDY DESIGN: Retrospective case series. METHODS: Data were collected from 4 veterinary hospitals. Follow-up data were obtained via a telephone questionnaire. Two multivariable logistic regression models were generated. Model 1 included all horses with synovial contamination following foot penetration undergoing surgical treatment, with the outcome variable being euthanasia during hospitalisation. Model 2 included all horses surviving anaesthesia, with the outcome variable being failure to return to pre-injury athletic function. RESULTS: Ninety-five horses were included. Overall, 56% of horses survived to discharge and 36% of horses returned to pre-injury athletic function. Model 1 included penetration of the central frog sulcus (odds ratio [OR] 10, 95% confidence interval [CI] 1.9-51.8), concurrent distal phalanx involvement (OR 32, 95% CI 2.6-101.9), increasing days to presentation (OR 1.2, 95% CI 1.0-1.3) and hospital. Model 2 included increasing days to presentation (OR 1.1, 95% CI 1.1-1.6), breed (OR 32, 95% CI 2.2-135.4), more than one surgery (OR 5.6, 95% CI 1.0-32.7) and hospital. CONCLUSIONS AND POTENTIAL RELEVANCE: Synovial involvement following solar foot penetration has a guarded prognosis for survival to discharge and a poor prognosis for return to pre-injury athletic function. Penetration of the central sulcus of the frog and distal phalanx involvement are associated with euthanasia during hospitalisation. Delayed referral and hospitalisation are associated with both euthanasia and failure to return to pre-injury athletic function. Breed and more than one surgery are associated with failure to return to pre-injury athletic function. These data may assist veterinary surgeons and owners to make evidence-based decisions when managing cases with synovial involvement following solar foot penetration.

Oxygen and pH-sensitivity of human osteoarthritic chondrocytes in 3-D alginate bead culture system.

OBJECTIVE: To identify the effect of alterations in physical parameters such as oxygen and pH on processes associated with cellular redox balance in osteoarthritic chondrocytes. METHOD: Human osteoarthritic chondrocytes (HOAC) were isolated from total knee arthroplasty samples and cultured in 3-D alginate beads in four different oxygen tensions (<1%, 2%, 5% and 21% O2), at pH 7.2 and 6.2 and in the presence or absence of 10 ng/ml, interleukin-1ß (IL-1ß). Cell viability, media glycosaminoglycan (GAG) levels, media nitrate/nitrate levels, active matrix metalloproteinase (MMP)-13 and intracellular adenosine triphosphate (ATPi) were measured over a 96-h time course. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential, intracellular pH and reduced/oxidised glutathione (GSH/GSSG) were additionally measured after 48-h incubation under these experimental conditions. RESULTS: Hypoxia (2% O2) and anoxia (<1% O2), acidosis (pH 6.2) and 10 ng/ml IL-1ß reduced HOAC cell viability and increased GAG media levels. Acidosis and IL-1ß increased nitrite/nitrate release, but increases were moderate at 2% O2 and significantly reduced at <1% O2. ATPi was significantly reduced following hypoxia and anoxia and acidosis. At 48 h cellular ROS levels were increased by acidosis and IL-1ß but reduced in hypoxia and anoxia. Mitochondrial membrane potential was reduced in low oxygen, acidosis and IL-1ß. Anoxia also resulted in intracellular acidosis. GSH/GSSG ratio was reduced in low oxygen conditions, acidosis and IL-1ß. CONCLUSIONS: This study shows that oxygen and pH affect elements of the redox system in HOAC including cellular anti-oxidants, mitochondrial membrane potential and ROS levels.

Deep digital flexor tendon injury within the hoof capsule; does lesion type or location predict prognosis?

The type and location of deep digital flexor tendon (DDFT) lesions may be important in predicting outcome. The objectives of this study were to determine the frequency of different types of DDFT lesions within the hoof capsule and to determine whether lesion type predicts return to athletic activity. Lesions of the DDFT were divided into: core lesions, dorsal border lesions and parasagittal splits. Lesion location was documented, and follow-up information was obtained by telephone survey at least 18 months after diagnosis. Of 168 horses with primary DDFT injury, 54 horses had dorsal border lesions, 59 had parasagittal splits and 55 had core lesions. Twenty-five per cent of all horses returned to previous levels of athletic activity within 18 months of MRI evaluation. Horses with complete splits or core lesions of the DDFT were significantly less likely to return to some level of athletic activity than horses with dorsal border lesions P<0.001. Dorsal border lesions of the DDFT appear to have a better prognosis than core lesions or parasagittal splits. This study provides additional information that may help clinicians predict the prognosis for different types of DDFT injury.

Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia.

Purinergic pathways are considered important in pain transmission, and P2X receptors are a key part of this system which has received little attention in the horse. The aim of this study was to identify and characterise the distribution of P2X receptor subtypes in the equine digit and associated vasculature and nervous tissue, including peripheral nerves, dorsal root ganglia and cervical spinal cord, using PCR, Western blot analysis and immunohistochemistry. mRNA signal for most of the tested P2X receptor subunits (P2X1-5, 7) was detected in all sampled equine tissues, whereas P2X6 receptor subunit was predominantly expressed in the dorsal root ganglia and spinal cord. Western blot analysis validated the specificity of P2X1-3, 7 antibodies, and these were used in immunohistochemistry studies. P2X1-3, 7 receptor subunits were found in smooth muscle cells in the palmar digital artery and vein with the exception of the P2X3 subunit that was present only in the vein. However, endothelial cells in the palmar digital artery and vein were positive only for P2X2 and P2X3 receptor subunits. Neurons and nerve fibres in the peripheral and central nervous system were positive for P2X1-3 receptor subunits, whereas glial cells were positive for P2X7 and P2X1 and 2 receptor subunits. This previously unreported distribution of P2X subtypes may suggest important tissue specific roles in physiological and pathological processes.

Feasibility of using microbiology diagnostic tests of moderate or high complexity at the point - of - care in a delivery suite.

Point-of-care testing (POCT) is one of the fastest growing sectors of laboratory diagnostics. Most tests in routine use are haematology or biochemistry tests that are of low complexity. Microbiology POCT has been constrained by a lack of tests that are both accurate and of low complexity. We describe our experience of the practical issues around using more complex POCT for detection of Group B streptococci (GBS) in swabs from labouring women. We evaluated two tests for their feasibility in POCT: an optical immune assay (Biostar OIA Strep B, Inverness Medical, Princetown, NJ) and a PCR (IDI-Strep B, Cepheid, Sunnyvale, CA), which have been categorised as being of moderate and high complexity, respectively. A total of 12 unqualified midwifery assistants (MA) were trained to undertake testing on the delivery suite. A systematic approach to the introduction and management of POC testing was used. Modelling showed that the probability of test results being available within a clinically useful timescale was high. However, in the clinical setting, we found it impossible to maintain reliable availability of trained testers. Implementation of more complex POC testing is technically feasible, but it is expensive, and may be difficult to achieve in a busy delivery suite.

Short-term temporal alterations in magnetic resonance signal occur in primary lesions identified in the deep digital flexor tendon of the equine digit.

REASONS FOR PERFORMING STUDY: Primary lesions of the deep digital flexor tendon (DDFT) within the digit are an important cause of lameness diagnosed using magnetic resonance imaging (MRI) but appearance of these lesions over time has not been documented. OBJECTIVES: To determine whether the magnetic resonance (MR) appearance of different primary DDFT lesions alter over a 6 month period and whether lesion type is a determinant of these changes. METHODS: Cases included had lameness attributable to a primary lesion involving the DDFT in the digit diagnosed on MRI. Lesions were typed into parasagittal, dorsal border and core lesions. Approximate volumes and intensities were quantified for each lesion type using T2* scan sequences. Follow-up examinations and measurements were repeated at 3 and 6 month periods following conservative management. RESULTS: Twenty-three horses fitted the inclusion criteria. Lesion distribution included: parasagittal (n = 7), dorsal border (n = 11) and core lesions (n = 5). No association was found between age of horse, degree of lameness and lesion type. Only dorsal border lesions showed statistically significant reduction both in volume (initial scan: 0.18 ± 0.14 cm(3) ) at 3 months (0.11 ± 0.10 cm(3) , P<0.05) and 6 months (0.05 ± 0.05 cm(3) , P<0.01) and ratiometric intensity (initial scan: 4.06 ± 1.54) at 6 months (2.00 ± 0.43; P<0.01). Parasagittal and core lesions showed no difference in lesion volume or ratiometric intensity. Lameness improved in all lesion types following conservative management. CONCLUSIONS: Dorsal border lesions of the DDFT show reduction in both volume and intensity whereas parasagittal and core lesions do not. POTENTIAL RELEVANCE: Lesion typing may be important in predicting lesion behaviour and short-term outcome using MR imaging.

Cost-effectiveness of rapid tests and other existing strategies for screening and management of early-onset group B streptococcus during labour.

OBJECTIVE: To determine the cost-effectiveness of alternative screening and prevention strategies, including rapid intrapartum testing, for prevention of early-onset neonatal group B streptococcus (GBS) infection in the UK. DESIGN: A decision model was developed to investigate the cost-effectiveness of screening and prevention strategies for GBS. A strategy of doing nothing was also considered. Deterministic and probabilistic sensitivity analyses were carried out. SETTING: Two large UK based obstetric units. PARTICIPANTS: Test accuracy data were obtained from a primary study of rapid tests at the onset of labour and risk factors from 1400 women. MAIN OUTCOME MEASURES: Incremental health sector costs per case of early-onset GBS death avoided. RESULTS: Compared with a strategy of do nothing, the incremental cost-effectiveness ratio was £32,000 per Early-Onset GBS Disease avoided and £427,000 per Early-Onset GBS Death avoided for the strategy of providing routine intrapartum antibiotic prophylaxis to all women without prior screening; Based on their current sensitivity, specificity and cost, screening using rapid tests was dominated by other more cost-effective strategies. CONCLUSIONS: The most cost-effective strategy was shown to be the provision of routine intrapartum antibiotic prophylaxis to all women without prior screening but, given broader concerns relating to antibiotic use, this is unlikely to be acceptable. In its absence, intrapartum antibiotic prophylaxis directed by screening with enriched culture becomes cost-effective. The current strategy of risk-factor-based screening is not cost-effective compared with screening based on culture.

Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by hyperosmotic loading.

OBJECTIVES: SOX9 is a transcription factor that is essential for cartilage extracellular matrix (ECM) formation. Osteoarthritis (OA) is characterised by a loss of cartilage ECM. In chondrocytes SOX9 gene expression is regulated by osmotic loading. Here we characterise SOX9 mRNA regulation through static and cyclical application of hyperosmotic conditions in normal and OA monolayer equine chondrocytes. Furthermore, we investigate whether extracellular signal-regulated protein kinase (ERK)1/2 mitogen-activated protein kinases (MAPK) pathways have a role in this regulation of SOX9. METHODS: Equine chondrocytes harvested from normal or OA joints were subjected to different osmotic loading patterns as either primary (P0) or passaged (P2) cells. The involvement of MEK-ERK signalling was demonstrated by using pharmacological inhibitors. In addition SOX9 gene stability was determined. Levels of transcripts encoding SOX9, Col2A1 and aggrecan were measured using qRT-PCR. De novo glycosaminoglycan synthesis of explants was determined with (35)S sulphate during static hyperosmolar loading. RESULTS: MEK-ERK signalling increases glycosaminoglycans (GAG) synthesis in explants. Static hyperosmotic conditions significantly reduced SOX9 mRNA in normal P2 and OA P0 but not normal P0 chondrocytes. SOX9 mRNA was stabilised by hyperosmotic conditions. Cyclical loading of normal P2 and OA P0 but not normal P0 cells led to an increase in SOX9 gene expression and this was prevented by MEK1/2 inhibition. CONCLUSIONS: The response to osmotic loading of SOX9 mRNA is dependent on the nature of the osmotic stimulation and the chondrocyte phenotype. This variation may be important in disease progression.

Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness.

OBJECTIVE: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. DESIGN: A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. SETTING: Two large obstetric units in the UK. PARTICIPANTS: Women booked for delivery at the participating units other than those electing for a Caesarean delivery. INTERVENTIONS: Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. MAIN OUTCOME MEASURES: The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. RESULTS: PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79-88%); vaginal swab 58% (52-64%); rectal swab 71% (66-76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85-89%); vaginal swab 92% (90-94%); rectal swab 92% (90-93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35-37 weeks' gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. CONCLUSIONS: Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35-37 weeks' gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.