Downstaging for hepatocellular cancer: Harm or benefit?

Downstaging of hepatocellular carcinoma (HCC) to enable liver transplantation has become an area of intense interest and research. It may allow a curative option in patients outside widely accepted transplantation criteria, with outcomes that, in some studies, are comparable to transplantation for patients within criteria. There have been conflicting opinions on the best downstaging protocols, criteria for downstaging eligibility and for assessment of response. We therefore aimed to review the literature and evidence for downstaging, as well as considering its drawbacks. Conclusion: Pooled analyses have suggested success in down staging in about half of patients treated, but with higher recurrence rates than patients initially within transplantation criteria. Studies with strict inclusion criteria and mandatory waiting time before transplantation reported survival equivalent to patients who did not require downstaging. In carefully selected patients, there is a role for down staging to provide the chance of transplantation and cure, with acceptable outcomes. Further multi center, well-designed studies are required to clarify who will mostly benefit. Until such data is available, downstaging criteria should be stated within transplantation programs and relevant decisions should be discussed by multidisciplinary teams

The incidence and clinical burden of respiratory syncytial virus disease identified through hospital outpatient presentations in Kenyan children

There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting. Methods We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence. Results Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively. Conclusion The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis

Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

Background: Our understanding of the transmission dynamics of respiratory syncytial virus (RSV) infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods: In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA) were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results: From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months), 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25) equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3), with a median duration of shedding of 4 days (IQR 2-6, range 1-14). Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86). The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion: We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

Improving Student Engagement in Veterinary Business Studies

In a densely packed veterinary curriculum, students may find it particularly challenging to engage in the less overtly clinical subjects, yet pressure from industry and an increasingly competitive employment market necessitate improved veterinary student education in business and management skills. We describe a curriculum intervention (formative reflective assignment) that optimizes workplace learning opportunities and aims to provide better student scaffolding for their in-context business learning. Students were asked to analyze a business practice they experienced during a period of extra-mural studies (external work placement). Following return to the college, they were then instructed to discuss their findings in their study group, and produce a group reflection on their learning. To better understand student engagement in this area, we analyzed individual and group components of the assignment. Thematic analysis revealed evidence of various depths of student engagement, and provided indications of the behaviors they used when engaging at different levels. Interactive and social practices (discussing business strategies with veterinary employees and student peers) appeared to facilitate student engagement, assist the perception of relevance of these skills, and encourage integration with other curriculum elements such as communication skills and clinical problem solving

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The duration of diarrhea and fever is associated with growth faltering in rural Malawian children aged 6-18 months

Nutrition support programs that only focus upon better complementary feeding remain an insufficient means of limiting growth faltering in vulnerable populations of children. To determine if symptoms of acute infections correlate with the incidence of growth faltering in rural Malawian children, the associations between fever, diarrhea, and cough with anthropometric measures of stunting, wasting, and underweight were investigated. Data were analyzed from a trial where 209 children were provided with adequate complementary food and followed fortnightly from 6-18 months of age. Linear mixed model analysis was used to test for associations. Diarrheal disease was inversely associated with changes in height-for-age Z-score (HAZ), mid-upper arm circumference Z-score (MUACZ), and weight-for-age Z-score (WAZ). Fever was also inversely associated with changes in MUACZ and WAZ. These results suggest that initiatives to reduce febrile and diarrheal diseases are needed in conjunction with improved complementary feeding to limit growth faltering in rural Malawi

Thirty years after Alma-Ata: a systematic review of the impact of community health workers delivering curative interventions against malaria, pneumonia and diarrhoea on child mortality and morbidity in sub-Saharan Africa

BACKGROUND: Over thirty years have passed since the Alma-Ata Declaration on primary health care in 1978. Many governments in the first decade following the declaration responded by developing national programmes of community health workers (CHWs), but evaluations of these often demonstrated poor outcomes. As many CHW programmes have responded to the HIV/AIDS pandemic, international interest in them has returned and their role in the response to other diseases should be examined carefully so that lessons can be applied to their new roles. Over half of the deaths in African children under five years of age are due to malaria, diarrhoea and pneumonia - a situation which could be addressed through the use of cheap and effective interventions delivered by CHWs. However, to date there is very little evidence from randomised controlled trials of the impacts of CHW programmes on child mortality in Africa. Evidence from non-randomised controlled studies has not previously been reviewed systematically. METHODS: We searched databases of published and unpublished studies for RCTs and non-randomised studies evaluating CHW programmes delivering curative treatments, with or without preventive components, for malaria, diarrhoea or pneumonia, in children in sub-Saharan Africa from 1987 to 2007. The impact of these programmes on morbidity or mortality in children under six years of age was reviewed. A descriptive analysis of interventional and contextual factors associated with these impacts was attempted. RESULTS: The review identified seven studies evaluating CHWs, delivering a range of interventions. Limited descriptive data on programmes, contexts or process outcomes for these CHW programmes were available. CHWs in national programmes achieved large mortality reductions of 63% and 36% respectively, when insecticide-treated nets and anti-malarial chemoprophylaxis were delivered, in addition to curative interventions. CONCLUSIONS: CHW programmes could potentially achieve large gains in child survival in sub-Saharan Africa if these programmes were implemented at scale. Large-scale rigorous studies, including RCTs, are urgently needed to provide policymakers with more evidence on the effects of CHWs delivering these interventions

Evaluation of cell-free DNA approaches for multi-cancer early detection

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test