Comparison of estimates of left ventricular ejection fraction using gated blood imagining

Serial measurement of left ventricular ejection fraction (L VEF) using GBP imaging is an established technique for monitoring L VEF in patients undergoing chemotherapy with cardio-toxic medication and in patients after heart transplants. Oncologists at our institution decide that cardio-toxic chemotherapy should be discontinued if the L VEF decreases by 10%, or if a value of 50% is reached. In patients with baseline L VEFs of less than 50% but greater than 30% therapy will be discontinued if the L VEF decreases by 10% or if a value of less than 30% is reached. This is in accordance with the guidelines set out by the Oxford Textbook ofOncology.3 In patients who have had heart transplants, GBP studies are used to monitor L VEF. If there is a decrease in L VEF, cardiologists may decide to start glucocoricosteroids for rejection. It is therefore imperative that serial studies on an individual patient are comparable. There are two software systems used in our nuclear medicine department; the Siemens system and the Hermes system. In a pilot study we found large differences between the L VEFs calculated by the two systems. This is consistent with the consensus in the literature that different software programs for processing GBP studies cannot be used interchangeably

Alcohol-based hand rub in the prevention of diarrhoea and respiratory-tract infection among children in community settings : a systematic review

Thesis (MCur)--Stellenbosch University, 2015.ENGLISH ABSTRACT: Annually more than 3.5 million children worldwide, less than five years of age die of diarrhoea and acute lower respiratory-tract infections. Over the last two decades, the care of pre-school children outside of their homes has become more common in most parts of the world and has contributed to an increased risk of respiratory-tract and gastrointestinal infections in children. Children attending day-care centres are at an increased risk for diarrhoea and respiratory-tract infections and hands are the primary vehicle for transmission of infectious diseases. Thus, hand hygiene is essential for preventing and controlling of infection in the health care and community settings. Waterless hand sanitizer as an alternative to hand washing was investigated. Rinse-free hand sanitizer programmes in the community may be effective, safe and feasible. The aim of the study was to systematically appraise evidence on the effect of alcohol-based hand rub in the prevention of diarrhoea and acute respiratory-tract infection among children aged five years and below in community settings. The primary outcome of the study was to assess the incidence of respiratory-tract infection and diarrhea. Diarrhoea is defined by the World Health Organization as the excretion of three or more loose or liquid stools per day (or more frequent excretion than is normal for the individual). The secondary outcome was to assess mortality, admission to hospital and duration of hospital stay. A comprehensive search for relevant studies was conducted on the following databases from 1990 to 2014: EMBASE, MEDLINE, CINAHL, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL). We searched the reference lists of all relevant articles and textbooks for more studies. Unpublished data previously presented at international and scientific meetings have been included in the review. Proceedings of international conferences on diarrhoea and respiratory-tract infection among children were searched for relevant articles. Subject experts were contacted. Two reviewers, Joelynn Steyn (JS) and Oswell Khondowe (OK) selected studies following a two-step study selection process. This review considered all published randomized controlled trials and quasi-experimental designs published from January 1990 to July 2014. The first step was the selection of studies based on titles and abstracts. Both reviewers selected eligible studies which met the set criteria. During the second step, both reviewers retrieved the full-text articles of the studies and assessed the methodological quality of the studies. Four studies were included in this review. The included studies met most of the quality assessment criteria as stipulated in the Cochrane risk assessment tool. Two studies were clusterrandomized controlled trials, one was a block randomized controlled trial and one was a randomized controlled trial. Disagreements were resolved by discussion and where a lack of consensus existed, consultation with a third reviewer occurred. The use of alcohol hand rub as compared to control interventions significantly reduced the incidence of diarrhoea in children (RR 0.79, 95% CI 0.63 to 0.99). Statistical heterogeneity was observed among the included studies (I²=69, p=0.04). However this review found no significant difference in respiratory-tract infections between intervention groups versus control as observed from the confidence interval (RR 0.98, 95% CI 0.90 to 1.07, p=0.63). The results should be interpreted with caution due to the limited number of studies conducted in communities with alcoholbased hand rub used by caregivers. Due to limited studies in this review, it makes it difficult to make strong conclusions on findings and to provide sufficient evidence to guide future research. We therefore recommend that more studies with high quality methodologies, using randomized controlled trial designs be conducted especially in poor resourced communities.AFRIKAANSE OPSOMMING: Meer as 3.5 miljoen kinders jonger as vyf jaar oud sterf jaarliks wêreldwyd as gevolg van diarree en akute laer respiratoriese lugweginfeksies. Oor die laaste dekades het die versorging van voorskoolse kinders buite hul tuiste meer algemeen geword in die meeste dele van die wêreld wat bygedra het tot ’n risiko in die toename van respiratoriese en spysverteringskanaalinfeksies by kinders. Kinders by dagsorgsentrums het ’n groter risiko vir diarree en respiratoriese lugweë infeksies want die oordra van siekte-infeksies word veral deur die hande wat as die primêre bron daarvan beskou word, gesien. Dus is hand-higiëne noodsaaklik om infeksies in gesondheidsorg en gemeenskapsentrums te voorkom en te beheer. ’n Waterlose hande-ontsmettingsmiddel as ’n alternatief om hande te was, is ondersoek. Spoelvrye hande-ontsmettingsmiddel programme in die gemeenskap mag effektief, veilig en uitvoerbaar wees. Die doel van die studie was om sistematies die geslaagdheid van bewyse op die effek van alkoholgebaseerde hande-smeermiddel in die voorkoming van diarree en akute lugweginfeksies by kinders 5 jaar en jonger in gemeenskapsentrums te ondersoek. Die primêre uitkoms van die studie was om die voorkoms van respiratoriese lugweginfeksie en diarree te asseseer. Diarree soos gedefinieer deur die WGO is die uitskeiding van drie of meer los- of waterige stoelgange per dag (of meer gereelde uitskeiding wat normaal vir die individu is). Die sekondêre uitkoms was om mortaliteit, toelating tot die hospitaal en duur van hospitaalverblyf te assesseer. ’n Omvattende soektog vir relevante studies was op die volgende databasisse van 2004-2014 uitgevoer: EMBASE, MEDLINE, CINAHL, Google Scholar en Cochrane Sentrale Register van Beheerde Toetse. Ons het die verwysingslyste van alle relevante artikels en handboeke vir meer navorsingstudies nagegaan. Ongepubliseerde data wat voorheen aangebied is by internasionale en wetenskaplike vergaderings, is ingesluit in die oorsig. Bevindings by internasionale konferensies oor diarree en lugweginfeksies by kinders was nagegaan in die soektog na relevante artikels. Onderwerpdeskundiges was gekontak. Die twee navorsers, Joelynn Steyn (JS) en Oswell Khondowe (OK) het studies geselekteer deur ’n twee-stap studieselekteringsproses te volg. Die oorsig het alle gepubliseerde, ewekansige gekontroleerde proewe en kwasi-eksperimenteerde studies oorweeg tussen Januarie 1990 en Julie 2014. Die eerste stap was die selektering van studies gebaseer op hul titels en opsommings. Beide navorsers het geskikte studies slegs geselekteer as die studie aan die bepaalde kriteria voldoen het. Tydens die tweede stap het beide navorsers die volledige artikels geneem van die studies geselekteer en die gehalte van die metodologie geassesseer. Vierstudies is in die oorsig ingesluit. Die ingeslote studies het aan die meeste vereistes soos deur die Cochrane risiko assesseringsinstrument gestipuleer voldoen. Twee studies was groep-ewekansige gekontroleerde proewe, een was ’n blok ewekansige gekontroleerde proef en een was ’n ewekansige gekontroleerde proef. Verskille is opgelos deur bespreking en waar daar onderbreking in konsensus was, het ’n konsultasie met ’n derde beoordelaar plaasgevind. Die gebruik van ’n alkohol handreiniger, soos vergelyk met kontrole-intervensies, het die voorkoms van diarree in kinders beduidend verminder (RR 0.79, 95% CI 0.63 to 0.99). Statistiese heterogeniteit is egter tussen die ingeslote studies waargeneem (I²=69, p=0.04). Hierdie studie het geen beduidende verskille in lugweg infeksies tussen die intervensiegroepe teenoor die kontrolegroep gevind nie soos waargeneem uit die vertroue interval (RR0.98, 95% CI 0.90 to 1.07, p=0.63). Die resultate moet met omsigtigheid geïnterpreteer word as gevolg van die beperkte aantal studies wat in gemeenskappe uitgevoer was met alkohol-gebasseerde handreiniger wat deur versorgers gebruik word. As gevolg van die beperkende aantal studies in hierdie studie, is dit moeilik om sterk gevolgtrekkings te maak op bevindinge en om voldoende bewyse te gee om toekomstige navorsing te rig. Ons beveel dus aan dat meer studies met hoë kwaliteit metodologie en wat ewekansige gekontroleerde proef-ontwerpe gebruik, uitgevoer word, veral in swak-toegeruste gemeenskappe. (RR0.98, 95% CI 0.90 to 1.07, p=0.63). Die resultate moet met omsigtigheid geïnterpreteer word as gevolg van die beperkte aantal studies wat gedoen is in gemeenskappe met alkohol

WHO guideline for non-surgical management of chronic primary low back pain in adults in primary and community care settings

The purpose of the guideline is to provide evidence-based recommendations on nonsurgical interventions for chronic primary LBP (CPLBP) in adults, including older people, that can be delivered in primary and community care settings to improve CPLBP-related health and well-being outcomes. For this reason, the guideline does not consider interventions typically delivered in secondary or tertiary care settings (e.g. surgical or other invasive procedures) or workplace interventions. The target audience is health workers of all disciplines working in the primary and community care settings. In this context, the guideline is intended to be discipline neutral. The guidelines will be of use to clinical staff including medical doctors, nurses, allied health workers including chiropractors, occupational therapists, physiotherapists, pharmacists, psychologists and community health workers, as well as public health programme and system managers

Spatial Network Mapping of Pulmonary Multidrug-Resistant Tuberculosis Cavities Using RNA Sequencing.

Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis.Objectives: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity.Methods: Biopsies were obtained from eight predetermined locations within lung cavities of patients with multidrug-resistant tuberculosis undergoing therapeutic surgical resection (n = 14) and healthy lung tissue from control subjects without tuberculosis (n = 10). RNA sequencing, immunohistochemistry, and bacterial load determination were performed at each cavity position. Differentially expressed genes were normalized to control subjects without tuberculosis, and ontologically mapped to identify a spatially compartmentalized pathophysiological map of the cavity. In silico perturbation using a novel distance-dependent dynamical sink model was used to investigate interactions between immune networks and bacterial burden, and to integrate these identified pathways.Measurements and Main Results: The median (range) lung cavity volume on positron emission tomography/computed tomography scans was 50 cm3 (15-389 cm3). RNA sequence reads (31% splice variants) mapped to 19,049 annotated human genes. Multiple proinflammatory pathways were upregulated in the cavity wall, whereas a downregulation "sink" in the central caseum-fluid interface characterized 53% of pathways including neuroendocrine signaling, calcium signaling, triggering receptor expressed on myeloid cells-1, reactive oxygen and nitrogen species production, retinoic acid-mediated apoptosis, and RIG-I-like receptor signaling. The mathematical model demonstrated that neuroendocrine, protein kinase C-θ, and triggering receptor expressed on myeloid cells-1 pathways, and macrophage and neutrophil numbers, had the highest correlation with bacterial burden (r > 0.6), whereas T-helper effector systems did not.Conclusions: These data provide novel insights into host immunity to Mycobacterium tuberculosis-related cavitation. The pathways defined may serve as useful targets for the design of host-directed therapies, and transmission prevention interventions

Effect of vaccination, border testing, and quarantine requirements on the risk of COVID-19 in New Zealand: A modelling study

We couple a simple model of quarantine and testing strategies for international travellers with a model for transmission of SARS-CoV-2 in a partly vaccinated population. We use this model to estimate the risk of an infectious traveller causing a community outbreak under various border control strategies and different levels of vaccine coverage in the population. Results are calculated from N = 100,000 independent realisations of the stochastic model. We find that strategies that rely on home isolation are significantly higher risk than the current mandatory 14-day stay in government-managed isolation. Nevertheless, combinations of testing and home isolation can still reduce the risk of a community outbreak to around one outbreak per 100 infected travellers. We also find that, under some circumstances, using daily lateral flow tests or a combination of lateral flow tests and polymerase chain reaction (PCR) tests can reduce risk to a comparable or lower level than using PCR tests alone. Combined with controls on the number of travellers from countries with high prevalence of COVID-19, our results allow different options for managing the risk of COVID-19 at the border to be compared. This can be used to inform strategies for relaxing border controls in a phased way, while limiting the risk of community outbreaks as vaccine coverage increases

Model-free estimation of COVID-19 transmission dynamics from a complete outbreak.

New Zealand had 1499 cases of COVID-19 before eliminating transmission of the virus. Extensive contract tracing during the outbreak has resulted in a dataset of epidemiologically linked cases. This data contains useful information about the transmission dynamics of the virus, its dependence on factors such as age, and its response to different control measures. We use Monte-Carlo network construction techniques to provide an estimate of the number of secondary cases for every individual infected during the outbreak. We then apply standard statistical techniques to quantify differences between groups of individuals. Children under 10 years old are significantly under-represented in the case data. Children infected fewer people on average and had a lower probability of transmitting the disease in comparison to adults and the elderly. Imported cases infected fewer people on average and also had a lower probability of transmitting than domestically acquired cases. Superspreading is a significant contributor to the epidemic dynamics, with 20% of cases among adults responsible for 65-85% of transmission. Subclinical cases infected fewer individuals than clinical cases. After controlling for outliers serial intervals were approximated with a normal distribution (μ = 4.4 days, σ = 4.7 days). Border controls and strong social distancing measures, particularly when targeted at superspreading, play a significant role in reducing the spread of COVID-19

Towards the validation of high-throughput sequencing (HTS) for routine plant virus diagnostics: measurement of variation linked to HTS detection of citrus viruses and viroids

CITATION: Bester, R., et al. 2021. Towards the validation of high-throughput sequencing (HTS) for routine plant virus diagnostics: measurement of variation linked to HTS detection of citrus viruses and viroids. Virology Journal, 18:61, doi:10.1186/s12985-021-01523-1.The original publication is available at https://virologyj.biomedcentral.comPublication of this article was funded by the Stellenbosch University Open Access FundBackground: High-throughput sequencing (HTS) has been applied successfully for virus and viroid discovery in many agricultural crops leading to the current drive to apply this technology in routine pathogen detection. The validation of HTS-based pathogen detection is therefore paramount. Methods: Plant infections were established by graft inoculating a suite of viruses and viroids from established sources for further study. Four plants (one healthy plant and three infected) were sampled in triplicate and total RNA was extracted using two different methods (CTAB extraction protocol and the Zymo Research Quick-RNA Plant Miniprep Kit) and sent for Illumina HTS. One replicate sample of each plant for each RNA extraction method was also sent for HTS on an Ion Torrent platform. The data were evaluated for biological and technical variation focussing on RNA extraction method, platform used and bioinformatic analysis. Results: The study evaluated the influence of different HTS protocols on the sensitivity, specificity and repeatability of HTS as a detection tool. Both extraction methods and sequencing platforms resulted in significant differences between the data sets. Using a de novo assembly approach, complemented with read mapping, the Illumina data allowed a greater proportion of the expected pathogen scaffolds to be inferred, and an accurate virome profile was constructed. The complete virome profile was also constructed using the Ion Torrent data but analyses showed that more sequencing depth is required to be comparative to the Illumina protocol and produce consistent results. The CTAB extraction protocol lowered the proportion of viroid sequences recovered with HTS, and the Zymo Research kit resulted in more variation in the read counts obtained per pathogen sequence. The expression profiles of reference genes were also investigated to assess the suitability of these genes as internal controls to allow for the comparison between samples across different protocols. Conclusions: This study highlights the need to measure the level of variation that can arise from the different variables of an HTS protocol, from sample preparation to data analysis. HTS is more comprehensive than any assay previously used, but with the necessary validations and standard operating procedures, the implementation of HTS as part of routine pathogen screening practices is possible.https://virologyj.biomedcentral.com/articles/10.1186/s12985-021-01523-1Publisher's versio

Reproducibility and Sensitivity of High-Throughput Sequencing (HTS)-Based Detection of Citrus Tristeza Virus and Three Citrus Viroids

The credibility of a pathogen detection assay is measured using specific parameters including repeatability, specificity, sensitivity, and reproducibility. The use of high-throughput sequencing (HTS) as a routine detection assay for viruses and viroids in citrus was previously evaluated and, in this study, the reproducibility and sensitivity of the HTS assay were assessed. To evaluate the reproducibility of HTS, the same plants assayed in a previous study were sampled again, one year later, and assessed in triplicate using the same analyses to construct the virome profile. The sensitivity of the HTS assay was compared to routinely used RT-PCR assays in a time course experiment, to compensate for natural pathogen accumulation in plants over time. The HTS pipeline applied in this study produced reproducible and comparable results to standard RT-PCR assays for the detection of CTV and three viroid species in citrus. Even though the limit of detection of HTS can be influenced by pathogen concentration, sample processing method and sequencing depth, detection with HTS was found to be either equivalent or more sensitive than RT-PCR in this study