The impact of HIV infection on tuberculosis transmission in a country with low tuberculosis incidence: a national retrospective study using molecular epidemiology

Background: HIV is known to increase the likelihood of reactivation of latent tuberculosis to active TB disease; however, its impact on tuberculosis infectiousness and consequent transmission is unclear, particularly in lowincidence settings. Methods: National surveillance data from England, Wales and Northern Ireland on tuberculosis cases in adults from 2010 to 2014, strain typed using 24-locus mycobacterial-interspersed-repetitive-units–variable-number-tandem-repeats was used retrospectively to identify clusters of tuberculosis cases, subdivided into ‘first’ and ‘subsequent’ cases. Firstly, we used zero-inflated Poisson regression models to examine the association between HIV status and the number of subsequent clustered cases (a surrogate for tuberculosis infectiousness) in a strain type cluster. Secondly, we used logistic regression to examine the association between HIV status and the likelihood of being a subsequent case in a cluster (a surrogate for recent acquisition of tuberculosis infection) compared to the first case or a non-clustered case (a surrogate for reactivation of latent infection). Results: We included 18,864 strain-typed cases, 2238 were the first cases of clusters and 8471 were subsequent cases. Seven hundred and fifty-nine (4%) were HIV-positive. Outcome 1: HIV-positive pulmonary tuberculosis cases who were the first in a cluster had fewer subsequent cases associated with them (mean 0.6, multivariable incidence rate ratio [IRR] 0.75 [0.65–0.86]) than those HIV-negative (mean 1.1). Extra-pulmonary tuberculosis (EPTB) cases with HIV were less likely to be the first case in a cluster compared to HIVnegative EPTB cases. EPTB cases who were the first case had a higher mean number of subsequent cases (mean 2.5, IRR (3.62 [3.12–4.19]) than those HIV-negative (mean 0.6). Outcome 2: tuberculosis cases with HIV co-infection were less likely to be a subsequent case in a cluster (odds ratio 0.82 [0.69–0.98]), compared to being the first or a non-clustered case. Conclusions: Outcome 1: pulmonary tuberculosis-HIV patients were less infectious than those without HIV. EPTB patients with HIV who were the first case in a cluster had a higher number of subsequent cases and thus may be markers of other undetected cases, discoverable by contact investigations. Outcome 2: tuberculosis in HIV-positive individuals was more likely due to reactivation than recent infection, compared to those who were HIV-negative

Predictors of Epstein-Barr virus serostatus in young people in England

BACKGROUND: Epstein-Barr virus (EBV) is an important human pathogen which causes lifelong infection of > 90% people globally and is linked to infectious mononucleosis (arising from infection in the later teenage years) and several types of cancer. Vaccines against EBV are in development. In order to determine the most cost-effective public health strategy for vaccine deployment, setting-specific data on the age at EBV acquisition and risk factors for early infection are required. Such data are also important to inform mathematical models of EBV transmission that can determine the required target product profile of vaccine characteristics. We thus aimed to examine risk factors for EBV infection in young people in England, in order to improve our understanding of EBV epidemiology and guide future vaccination strategies. METHODS: The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected via questionnaires and blood samples. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for EBV and cytomegalovirus (CMV) antibodies. We undertook descriptive and regression analyses of EBV seroprevalence and risk factors for infection. RESULTS: Demographic data and serostatus were available for 732 individuals. EBV seroprevalence was strongly associated with age, increasing from 60.4% in 11-14 year olds throughout adolescence (68.6% in 15-18 year olds) and stabilising by early adulthood (93.0% in those aged 22-24 years). In univariable and multivariable logistic regression models, ethnicity was associated with serostatus (adjusted odds ratio for seropositivity among individuals of other ethnicity versus white individuals 2.33 [95% confidence interval 1.13-4.78]). Smoking was less strongly associated with EBV seropositivity. CONCLUSIONS: By the age of 11 years, EBV infection is present in over half the population, although age is not the only factor associated with serostatus. Knowledge of the distribution of infection in the UK population is critical for determining future vaccination policies, e.g. comparing general versus selectively targeted vaccination strategies

Surgical and conservative treatment of patients with congenital scoliosis: α search for long-term results

<p>Abstract</p> <p>Background</p> <p>In view of the limited data available on the conservative treatment of patients with congenital scoliosis (CS), early surgery is suggested in mild cases with formation failures. Patients with segmentation failures will not benefit from conservative treatment. The purpose of this review is to identify the mid- or long-term results of spinal fusion surgery in patients with congenital scoliosis.</p> <p>Methods</p> <p>Retrospective and prospective studies were included, reporting on the outcome of surgery in patients with congenital scoliosis. Studies concerning a small numbers of cases treated conservatively were included too. We analyzed mid-term (5 to 7 years) and long-term results (7 years or more), both as regards the maintenance of the correction of scoliosis and the safety of instrumentation, the early and late complications of surgery and their effect on quality of life.</p> <p>Results</p> <p>A small number of studies of surgically treated patients were found, contained follow-up periods of 4-6 years that in the most cases, skeletal maturity was not yet reached, and few with follow-up of 36-44 years. The results of bracing in children with congenital scoliosis, mainly in cases with failure of formation, were also studied.</p> <p>Discussion</p> <p>Spinal surgery in patients with congenital scoliosis is regarded in short as a safe procedure and should be performed. On the other hand, early and late complications are also described, concerning not only intraoperative and immediate postoperative problems, but also the safety and efficacy of the spinal instrumentation and the possibility of developing neurological disorders and the long-term effect these may have on both lung function and the quality of life of children.</p> <p>Conclusions</p> <p>Few cases indicate the long-term results of surgical techniques, in the natural progression of scoliosis. Similarly, few cases have been reported on the influence of conservative treatment.</p> <p>In conclusion, patients with segmentation failures should be treated surgically early, according to the rate of deformity formation and certainly before the pubertal growth spurt to try to avoid cor- pulmonale, even though there is lack of evidence for that in the long-term. Furthermore, in patients with formation failures, further investigation is needed to document where a conservative approach would be necessary.</p

Introduction to the "Scoliosis" Journal Brace Technology Thematic Series: increasing existing knowledge and promoting future developments

Bracing is the main non-surgical intervention in the treatment of idiopathic scoliosis during growth, in hyperkyphosis (and Scheuermann disease) and occasionally for spondylolisthesis; it can be used in adult scoliosis, in the elderly when pathological curves lead to a forward leaning posture or in adults after traumatic injuries. Bracing can be defined as the application of external corrective forces to the trunk; rigid supports or elastic bands can be used and braces can be custom-made or prefabricated. The state of research in the field of conservative treatment is insufficient and while it can be stated that there is some evidence to support bracing, we must also acknowledge that today we do not have a common and generally accepted knowledge base, and that instead, individual expertise still prevails, giving rise to different schools of thought on brace construction and principles of correction. The only way to improve the knowledge and understanding of brace type and brace function is to establish a single and comprehensive source of information about bracing. This is what the Scoliosis Journal is going to do through the "Brace Technology" Thematic Series, where technical papers coming from the different schools will be published

7th SOSORT consensus paper: conservative treatment of idiopathic & Scheuermann's kyphosis

<p>Abstract</p> <p/> <p>Thoracic hyperkyphosis is a frequent problem and can impact greatly on patient's quality of life during adolescence. This condition can be idiopathic or secondary to Scheuermann disease, a disease disturbing vertebral growth. To date, there is no sound scientific data available on the management of this condition. Some studies discuss the effects of bracing, however no guidelines, protocols or indication's of treatment for this condition were found. The aim of this paper was to develop and verify the consensus on managing thoracic hyperkyphosis patients treated with braces and/or physiotherapy.</p> <p>Methods</p> <p>The Delphi process was utilised in four steps gradually modified according to the results of a set of recommendations: we involved the SOSORT Board twice, then all SOSORT members twice, with a Pre-Meeting Questionnaire (PMQ), and during a Consensus Session at the SOSORT Lyon Meeting with a Meeting Questionnaire (MQ).</p> <p>Results</p> <p>There was an unanimous agreement on the general efficacy of bracing and physiotherapy for this condition. Most experts suggested the use of 4-5 point bracing systems, however there was some controversy with regards to physiotherapeutic aims and modalities.</p> <p>Conclusion</p> <p>The SOSORT panel of experts suggest the use of rigid braces and physiotherapy to correct thoracic hyperkyphosis during adolescence. The evaluation of specific braces and physiotherapy techniques has been recommended.</p

Social acceptability of treatments for adolescent idiopathic scoliosis: a cross-sectional study

BACKGROUND: There are no data on social acceptability of scoliosis. Aim. To elicit evidence-based opinions on therapeutic strategies for adolescent idiopathic scoliosis in a sample of families with not affected children, so to understand the social perception of this issue. METHODS: Design. Cross-sectional study. Setting. Secondary schools in 4 northern Italian regions. Participants. Parents of children in the age group at risk of and not affected by scoliosis (Pre-test group = 100, Study group = 3,162). Interventions. Questionnaire: five specific and evidence-based questions regarding scoliosis treatment options and a socio-demographic section. Methodology. "Role-playing" in which it was required to normal people to answer what they would have chosen if they had been in the situation proposed. Main outcome measures. Perception of acceptability of treatments for adolescent idiopathic scoliosis in the general population (social acceptability) RESULTS: The families support the use of screening (94.8%) at school, immediate bracing (76.4%) for scoliosis with a 60% risk of progression, but also therapeutic exercises (86.9%) in cases with a 25% risk of progression. CONCLUSION: There is a growing tendency to consider not only the efficacy, effectiveness and efficiency of treatments, but also their acceptability. This patient-centred aspect is especially more important in areas (like adolescent idiopathic scoliosis) in which there is some evidence on the efficacy of treatments, but not strong and definitive (RCTs). Adolescent idiopathic scoliosis treatments should thus be carefully considered also in the light of their social acceptability

Juvenile idiopathic scoliosis treated with posterior arthrodesis and segmental pedicle screw instrumentation before the age of 9 years: a 5-year follow-up

<p>Abstract</p> <p>Study design</p> <p>Retrospective study.</p> <p>Objective</p> <p>To evaluate the radiological results of fusion with segmental pedicle screw fixation in juvenile idiopathic scoliosis with a minimum 5-year follow-up.</p> <p>Summary of background data</p> <p>Progression of spinal deformity after posterior instrumentation and fusion in immature patients has been reported by several authors. Segmental pedicle screw fixation has been shown to be effective in controlling both coronal and sagittal plane deformities. However, there is no long term study of fusion with segmental pedicle screw fixation in these group of patients.</p> <p>Methods</p> <p>Seven patients with juvenile idiopathic scoliosis treated by segmental pedicle screw fixation and fusion were analyzed. The average age of the patients was 7.4 years (range 5–9 years) at the time of the operation. All the patients were followed up 5 years or more (range 5–8 years) and were all Risser V at the most recent follow up. Three dimensional reconstruction of the radiographs was obtained and 3DStudio Max software was used for combining, evaluating and modifying the technical data derived from both 2d and 3d scan data.</p> <p>Results</p> <p>The preoperative thoracic curve of 56 ± 15° was corrected to 24 ± 17° (57% correction) at the latest follow-up. The lumbar curve of 43 ± 14° was corrected to 23 ± 6° (46% correction) at the latest follow-up. The preoperative thoracic kyphosis of 37 ± 13° and the lumbar lordosis of 33 ± 13° were changed to 27 ± 13° and 42 ± 21°, respectively at the latest follow-up. None of the patients showed coronal decompensation at the latest follow-up. Four patients had no evidence of crankshaft phenomenon. In two patients slight increase in Cobb angle at the instrumented segments with a significant increase in AVR suggesting crankshaft phenomenon was seen. One patient had a curve increase in both instrumented and non instrumented segments due to incorrect strategy.</p> <p>Conclusion</p> <p>In juvenile idiopathic curves of Risser 0 patients with open triradiate cartilages, routine combined anterior fusion to prevent crankshaft may not be warranted by posterior segmental pedicle screw instrumentation.</p

PuLSE:Quality control and quantification of peptide sequences explored by phage display libraries

The design of highly diverse phage display libraries is based on assumption that DNA bases are incorporated at similar rates within the randomized sequence. As library complexity increases and expected copy numbers of unique sequences decrease, the exploration of library space becomes sparser and the presence of truly random sequences becomes critical. We present the program PuLSE (Phage Library Sequence Evaluation) as a tool for assessing randomness and therefore diversity of phage display libraries. PuLSE runs on a collection of sequence reads in the fastq file format and generates tables profiling the library in terms of unique DNA sequence counts and positions, translated peptide sequences, and normalized 'expected' occurrences from base to residue codon frequencies. The output allows at-a-glance quantitative quality control of a phage library in terms of sequence coverage both at the DNA base and translated protein residue level, which has been missing from toolsets and literature. The open source program PuLSE is available in two formats, a C++ source code package for compilation and integration into existing bioinformatics pipelines and precompiled binaries for ease of use

Domain-and species-specific monoclonal antibodies recognize the Von Willebrand Factor-C domain of CCN5

The CCN family of proteins typically consists of four distinct peptide domains: an insulin-like growth factor binding protein-type (IGFBP) domain, a Von Willebrand Factor C (VWC) domain, a thrombospondin type 1 repeat (TSP1) domain, and a carboxy-terminal (CT) domain. The six family members participate in many processes, including proliferation, motility, cell-matrix signaling, angiogenesis, and wound healing. Accumulating evidence suggests that truncated and alternatively spliced isoforms are responsible for the diverse functions of CCN proteins in both normal and pathophysiologic states. Analysis of the properties and functions of individual CCN domains further corroborates this idea. CCN5 is unique among the CCN family members because it lacks the CT-domain. To dissect the domain functions of CCN5, we are developing domain-specific mouse monoclonal antibodies. Monoclonal antibodies have the advantages of great specificity, reproducibility, and ease of long-term storage and production. In this communication, we injected mixtures of GST-fused rat CCN5 domains into mice to generate monoclonal antibodies. To identify the domains recognized by the antibodies, we constructed serial expression plasmids that express dual-tagged rat CCN5 domains. All of the monoclonal antibodies generated to date recognize the VWC domain, indicating it is the most highly immunogenic of the CCN5 domains. We characterized one particular clone, 22H10, and found that it recognizes mouse and rat CCN5, but not human recombinant CCN5. Purified 22H10 was successfully applied in Western Blot analysis, immunofluorescence of cultured cells and tissues, and immunoprecipitation, indicating that it will be a useful tool for domain analysis and studies of mouse-human tumor models