Canterbury index : an accurate predictor of fracture re-displacement?

PURPOSE: Paediatric forearm fractures are commonly seen and treated by closed reduction and plaster cast application in theatre. Historically cast application has been subjectively evaluated for its adequacy in maintaining fracture reduction. More recently emphasis has been placed on objectively evaluating the adequacy of cast application using indicators such as the Canterbury index (CI). The CI has been used in predicting post-reduction, re-displacement risk of patients by expressing the cast and padding indexes as a ratio. The CI has been criticised for not including cast three-point pressure, fracture personality, lack of standardisation of X-ray views as well as practical requirement of physical measurement using rulers. The aim of this study was to determine whether subjective evaluation of these indices, before and after a tutorial on the CI, was accurate in predicting a patient’s ultimate risk of re-displacement, following reduction and casting. In addition, we aimed to determine whether objective evaluation of these indices by measurement on the hospital’s digital X-ray system correlated with the final fracture outcome post-reduction. MATERIALS AND METHODS: A retrospective study was done on a sample of 11 patients during the period May 2010 to July 2011 at Steve Biko Academic Hospital. In total, 44 X-rays/fluoroscopy views were subjectively evaluated by 20 registrars and eight consultants for possible fracture re-displacement, before and after a tutorial on the CI. Five consultants and 10 registrars each measured 22 cast, padding and CIs on the digital X-ray system. RESULTS: A formal tutorial did not produce an increase in subjective predictive accuracy. Pre- and post-tutorial observed agreement was seldom better than agreement by chance alone. Poor strength of agreement (κ <0.20) was found in all groups, irrespective of level of displacement, imaging modality, level of orthopaedic training and tutorial attendance. Objective measurement of the indexes all had insignificant p-values for comparing groups, indicating that there was no correlation between the measured indexes and the final outcome irrespective of the level of fracture, imaging modality and level of orthopaedic training. Shortcomings were variable co-operation from participants and non-standardisation of X-rays. CONCLUSION: In our hospital setting, no clinical value for the subjective and/or objective use of the CI could be found. Subjective agreement was almost the same as expected agreement and objective measurement indicated no correlation with the fracture outcome. It is suggested that patients following closed reduction of forearm fractures be followed up within the first three days, and regularly thereafter, as there is currently no ideal system to predict re-displacement. Further studies are needed to validate the CI by standardisation of X-rays.http://www.charpublications.co.za/C_JournalsORTH.as

VALIDATE:Exploiting the synergy between complex intracellular pathogens to expedite vaccine research and development for tuberculosis, leishmaniasis, melioidosis and leprosy

For several complex intracellular pathogens, we have an urgent need for effective vaccines and yet there are common barriers to vaccine development. These diseases, including tuberculosis, leishmaniasis, leprosy and melioidosis, cause a huge burden of disease and disproportionately affect low and middle income countries. They are therefore often neglected due to the marginalisation of affected populations and the poor predicted commercial return on investment. Barriers to vaccine development include an incomplete understanding of protective immunity and translation from the bench into clinical vaccine trials. The current linear approach to vaccine research and development for these pathogens, which involves basic research, vaccine design, and vaccine evaluation in preclinical challenge models and clinical trials, is inefficient for these complex intracellular pathogens. We have established a Global Challenges Research Fund Network for VAccine deveLopment for complex Intracellular neglecteD pAThogEns, “VALIDATE”, where we aim to adopt a more flexible, integrated cross-pathogen approach to accelerate vaccine research and clinical development for these four pathogens, by cross-pathogen analyses, cross-discipline collaborations, and repeated integration of data from human and animal studies. This network provides a unique opportunity to bring together individuals working on four exemplar complex intracellular neglected pathogens (M.tb, Leishmania spp., B. pseudomallei and M.leprae), which share a common lifestyle as pathogens of macrophages, induce similar end-stage pathologies and alter host immune and metabolic responses. The horizontal collaborations established throughout this network, together with the provision of a protected environment for early data sharing, will exploit these biological synergies. By interrogating mechanisms that lead from infection to disease, we will be able to develop common vaccine development strategies for these and other complex intracellular pathogens. Keyword

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial

Background: Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. Methods: This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18–50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. Findings: Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2–11] vs 4% [1–13], p=0·62; respiratory 7% [1–19] vs 4% [1–9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5–17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [−1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported—a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. Interpretation: This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Assessment of monitoring and evaluation of non-financial performance of provincial departments in the province of the Eastern Cape with special reference to its impact on service delivery

In this research study an investigation was launched into the monitoring and evaluation system that the government introduced to monitor and evaluate the performance information produced by the Provincial Government Departments on the implementation of their annual performance plans. The Government Departments obtain budget approval from the Legislature and submit their three-year performance plans with their budgets. The government realized that service delivery was not improving against the back drop of annually increasing the budgets. The monitoring and evaluation system was introduced to assist the Government Departments with the implementation of their annual performance plans. Monitoring and evaluation serves as a control measure and deviations can be detected from the planned outputs of the Government Departments. Corrective measures must be instituted that will have the effect that the Government Departments meet the targets set in the indicators as approved in the annual performance plans. A literature review was conducted on monitoring and evaluation regarding the ideal manner in which it should be performed. The South African Government introduced a number of discussion documents from the Presidency and National Treasury on monitoring and evaluation. Several authors raised their views on the matter and it was captured in the research study. The methodology followed was based on the Systems Theory and a questionnaire was prepared and circulated amongst Political Office Bearers and Chief Officials in the Provincial Government Departments in the Eastern Cape on the issues that was researched. Interviews were conducted with selected participants to gain clarity on specific issues related to the questionnaire. The official annual report issued by the Auditor General to the Provincial Legislature served as official document in the research study. The data collected from the questionnaire, interviews and official documentation was analyzed and graphs were drawn and deductions were made from the results. Findings and recommendations were made from the data collected and a summary was compiled of the issues raised in the research study

Effects of environmental enrichment on cognitive performance of pigs in a spatial holeboard discrimination task

This study investigated the effects of environmental enrichment on the cognitive performance of female conventional farm (growing) pigs in a spatial holeboard task. Ten pairs of littermates matched for weight were used. From each litter, one piglet was randomly assigned to a barren environment; the other was assigned to an enriched environment from 4 weeks of age. The enriched environment was double the size of the barren environment, had a floor covered with straw, a rooting area filled with peat, and one of the four different enrichment toys which were exchanged daily. Starting at 11 weeks of age, all pigs were tested in a spatial holeboard discrimination task in which 4 out of 16 holes were baited. Furthermore, basal salivary cortisol levels of all pigs were determined after the end of all testing. All pigs were able to acquire the pattern of baited holes (acquisition phase, 40 trials) and the diagonally mirrored pattern (reversal phase, 20 trials). During the acquisition phase, the reference memory performance of the enriched-housed pigs was better than that of their barren-housed littermates, i.e. they reduced visits to the unbaited set of holes. During the reversal phase, enriched-housed pigs had a better general working memory performance than the barren-housed pigs as indicated by reduced revisits to holes already visited during a trial, irrespective of whether they were of the baited or the unbaited set. The enriched-housed pigs also searched for the hidden bait faster during both phases. The environments did not affect basal salivary cortisol levels. In conclusion, environmental enrichment slightly improved the cognitive performance of pigs in a spatial learning task. We hypothesise that the long period of habituation to and testing in the holeboard acted as enrichment that partially reduced the effects of barren housing