Information provision in cervical screening in Australia

• The National Cervical Screening Program, and associated state and territory organisations, are responsible for promoting cervical screening. Communication via multiple media channels encourages women to be screened. • Some communications are not clear about misrepresent the risk of cervical cancer and the protective capacity and reliability of the Pap smear. The potential harms of screening are rarely presented. • Participation is a key performance indicator for the Program. • Women receive Pap tests from clinicians, mostly general practitioners (GPs) who often screen opportunistically during already-busy appointments. Incentive Payments encourage high screening rates. • Consent is an important ethical principle in the delivery of all health care. Provision of material information is one of the elements of valid consent. • The combination of arguably ambiguous misleading communications, screening participation targets, and opportunistic testing under time pressure seems likely to undermine opportunities for women participating in the cervical cancer screening program to be informed. • Of particular concern are women who are less likely to benefit, women who are more likely to experience harm, and some groups of disadvantaged women. • Improved communications could include the absolute risk of cervical cancer and the morbidity and mortality benefits and harms of screening. Screening programs internationally have begun providing such information. • Performance indicators could value evidence of discussion or informing. • Areas for further research include the appropriate roles of the program, screeners, and individuals in providing and seeking information. Such work would identify the optimum method for informing women in the screening process

‘Organised’ cervical screening 45 years on: How consistent are organised screening practices?

Organised screening programmes have been remarkably successful in reducing incidence and mortality from cervical cancer, while opportunistic screening varies in its effectiveness. Experts recommend that cervical screening or HPV testing be carried out only in the context of an organised programme. We sought to answer the following study questions: What does it mean for a cervical screening programme to be organised? Is there a place for opportunistic screening (in an organised programme)? We reviewed 154 peer-reviewed papers on organised and opportunistic approaches to cervical screening published between 1970 and 2014 to understand how the term ‘organised’ is used, formally and in practice. We found that despite broad recognition of a prescriptive definition of organisation, in practice the meaning of organisation is much less clear. Our review revealed descriptions of organised programmes that differ significantly from prescribed norms and from each other, and a variety of ways that opportunistic and organised programmes intersect. We describe the breadth of the variation in cervical cancer screening programmes and examine the relationships and overlaps between organised and opportunistic screening. Implications emerging from the review include the need to better understand the breadth of organisation in practice, the drivers and impacts of opportunistic screening and the impact of opportunistic screening on population programme outcomes. Appreciation of the complexity of cervical screening programmes will benefit both screeners and women as programmes are changed to reflect a partially vaccinated population, new evidence and new technologies

KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria.

Plasmodium falciparum malaria causes half a million deaths per year, with up to 9% of this mortality caused by cerebral malaria (CM). One of the major processes contributing to the development of CM is an excess of host inflammatory cytokines. Recently K+ signaling has emerged as an important mediator of the inflammatory response to infection; we therefore investigated whether mice carrying an ENU induced activation of the electroneutral K+ channel KCC1 had an altered response to Plasmodium berghei. Here we show that Kcc1M935K/M935K mice are protected from the development of experimental cerebral malaria, and that this protection is associated with an increased CD4+ and TNFa response. This is the first description of a K+ channel affecting the development of experimental cerebral malaria

Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency.

In this study, we performed a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here, we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued

Methods for identifying surgical wound infection after discharge from hospital: a systematic review.

Background: Wound infections are a common complication of surgery that add significantly to the morbidity of patients and costs of treatment. The global trend towards reducing length of hospital stay post-surgery and the increase in day case surgery means that surgical site infections (SSI) will increasingly occur after hospital discharge. Surveillance of SSIs is important because rates of SSI are viewed as a measure of hospital performance, however accurate detection of SSIs post-hospital discharge is not straightforward. Methods: We conducted a systematic review of methods of post discharge surveillance for surgical wound infection and undertook a national audit of methods of post-discharge surveillance for surgical site infection currently used within United Kingdom NHS Trusts. Results: Seven reports of six comparative studies which examined the validity of post-discharge surveillance methods were located; these involved different comparisons and some had methodological limitations, making it difficult to identify an optimal method. Several studies evaluated automated screening of electronic records and found this to be a useful strategy for the identification of SSIs that occurred post discharge. The audit identified a wide range of relevant post-discharge surveillance programmes in England, Scotland and Wales and Northern Ireland; however, these programmes used varying approaches for which there is little supporting evidence of validity and/or reliability. Conclusion: In order to establish robust methods of surveillance for those surgical site infections that occur post discharge, there is a need to develop a method of case ascertainment that is valid and reliable post discharge. Existing research has not identified a valid and reliable method. A standardised definition of wound infection ( e. g. that of the Centres for Disease Control) should be used as a basis for developing a feasible, valid and reliable approach to defining post discharge SSI. At a local level, the method used to ascertain post discharge SSI will depend upon the purpose of the surveillance, the nature of available routine data and the resources available

Effects of steady state free precession parameters on cardiac mass, function, and volumes

G0400444/Medical Research Council/United Kingdom Wellcome Trust/United Kingdo

Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics

Abstract Background Chiari-like malformation in the Cavalier King Charles Spaniel is a herniation of the cerebellum and brainstem into or through the foramen magnum. This condition predisposes to Syringomyelia; fluid filled syrinxes within the spinal cord. The resulting pathology in spinal cord and cerebellum create neuropathic pain and changes in gait. This study aims to quantify the changes in gait for Cavalier King Charles Spaniel with Chiari-like malformation and Syringomyelia. Methods We compared Cavalier King Charles Spaniel with Chiari-like malformation with (n = 9) and without (n = 8) Syringomyelia to Border Terriers (n = 8). Two video cameras and manual tracking was used to quantify gait parameters. Results and conclusions We found a significant increase in coefficient of variation for the spatio-temporal characteristics and ipsilateral distance between paws and a wider base of support in the thoracic limbs but not in the pelvic limbs for Cavalier King Charles Spaniels compared with the border terrier

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response