A serological investigation of caseous lymphadenitis in four flocks of sheep

A double antibody sandwich ELISA developed by ID-DLO, Lelystad to detect Corynebocterium pseudotuberculosis infection was used on 329 sheep from four pedigree Suffolk flocks in which clinical cases of caseous lymphadenitis (CLA) had occurred. At subsequent necropsy, typical CLA lesions were seen in 133 sheep, and the diagnosis was confirmed on culture. Lesions were most commonly seen in lungs (n = 46), parotid lymph nodes (n = 44), prescapular lymph nodes (n = 38) and mediastinal lymph nodes (n = 31). The sensitivity of the ELISA test for detecting culture-positive sheep was 0.88, while the specificity of the test was 0.55. The antibody ELISA detected 87.5 per cent of sheep that had CLA lesions restricted to internal organs only. It was concluded that the ELISA test has a valuable role in detecting sheep with both clinical and subclinical CLA

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Benefit of anti-TNF therapy in rheumatoid arthritis patients with moderate disease activity

Objectives. Anti-TNF therapy has improved outcomes for patients with highly active RA. Less is known about its effectiveness in patients with lower disease activity. The aim of this analysis is to compare the response to anti-TNF therapy between RA patients with high (DAS28 > 5.1) and moderate (DAS28 > 3.2–5.1) disease activity. Methods. A total of 4687 anti-TNF and 344 DMARD patients with high disease activity despite treatment with two standard DMARDs (including MTX) and 224 anti-TNF- and 300 DMARD-treated patients with moderate disease activity were selected from the British Society For Rheumatology Biologics Register. Mean change in HAQ over the first 12 months of enrolment was compared first between anti-TNF-treated and untreated patients in each DAS28 group, and then between anti-TNF-treated patients in the moderate and high DAS28 groups, using doubly robust estimates, adjusting for age, gender, disease duration, baseline HAQ and DAS28 score, number of previous DMARDs and steroid use. Results. Compared with anti-TNF-untreated patients within each DAS group, treated patients were younger, had higher DAS28 and HAQ and had failed a higher number of previous DMARDs. The mean adjusted change in HAQ over 12 months was similar in anti-TNF-treated patients with moderate and high disease activity at baseline: moderate −0.26 (95% CI −0.35, −0.16), high −0.28 (95% CI −0.34, −0.23) and mean difference −0.03 (95% CI −0.14, 0.08). Conclusions. Improvement in HAQ score 12 months after start of anti-TNF therapy was not dependent on baseline DAS28 scores, suggesting that substantial benefits may also be gained by treating those with moderately active disease despite standard DMARD therapy

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases : subgroup analyses of the RESTART randomised, open-label trial

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627. Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05). Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision. Funding: British Heart Foundation