Infrequent Expression of the Cancer-Testis Antigen, PASD1, in Ovarian Cancer

Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I), there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs), such as Per ARNT SIM (PAS) domain containing 1 (PASD1), are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I (n = 164) and stage II (n = 14) disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue.

Establishing the validity of English GP Patient Survey items evaluating out-of-hours care

Background A 2014 national audit used the English General Practice Patient Survey (GPPS) to compare service users’ experience of out-of-hours general practitioner (GP) services, yet there is no published evidence on the validity of these GPPS items. Objectives Establish the construct and concurrent validity of GPPS items evaluating service users’ experience of GP out-of-hours care. Methods Cross-sectional postal survey of service users (n=1396) of six English out-of-hours providers. Participants reported on four GPPS items evaluating out-of-hours care (three items modified following cognitive interviews with service users), and 14 evaluative items from the Out-of-hours Patient Questionnaire (OPQ). Construct validity was assessed through correlations between any reliable (Cochran's α>0.7) scales, as suggested by a principal component analysis of the modified GPPS items, with the ‘entry access’ (four items) and ‘consultation satisfaction’ (10 items) OPQ subscales. Concurrent validity was determined by investigating whether each modified GPPS item was associated with thematically related items from the OPQ using linear regressions. Results The modified GPPS item-set formed a single scale (α=0.77), which summarised the two-component structure of the OPQ moderately well; explaining 39.7% of variation in the ‘entry access’ scores (r=0.63) and 44.0% of variation in the ‘consultation satisfaction’ scores (r=0.66), demonstrating acceptable construct validity. Concurrent validity was verified as each modified GPPS item was highly associated with a distinct set of related items from the OPQ. Conclusions Minor modifications are required for the English GPPS items evaluating out-of-hours care to improve comprehension by service users. A modified question set was demonstrated to comprise a valid measure of service users’ overall satisfaction with out-of-hours care received. This demonstrates the potential for the use of as few as four items in benchmarking providers and assisting services in identifying, implementing and assessing quality improvement initiatives.

The use of patient experience survey data by out-of-hours primary care services: a qualitative interview study

Background English National Quality Requirements mandate out-of-hours primary care services to routinely audit patient experience, but do not state how it should be done.

Objectives We explored how providers collect patient feedback data and use it to inform service provision. We also explored staff views on the utility of out-of-hours questions from the English General Practice Patient Survey (GPPS).

Methods A qualitative study was conducted with 31 staff (comprising service managers, general practitioners and administrators) from 11 out-of-hours primary care providers in England, UK. Staff responsible for patient experience audits within their service were sampled and data collected via face-to-face semistructured interviews.

Results Although most providers regularly audited their patients’ experiences by using patient surveys, many participants expressed a strong preference for additional qualitative feedback. Staff provided examples of small changes to service delivery resulting from patient feedback, but service-wide changes were not instigated. Perceptions that patients lacked sufficient understanding of the urgent care system in which out-of-hours primary care services operate were common and a barrier to using feedback to enable change. Participants recognised the value of using patient experience feedback to benchmark services, but perceived weaknesses in the out-of-hours items from the GPPS led them to question the validity of using these data for benchmarking in its current form.

Conclusions The lack of clarity around how out-of-hours providers should audit patient experience hinders the utility of the National Quality Requirements. Although surveys were common, patient feedback data had only a limited role in service change. Data derived from the GPPS may be used to benchmark service providers, but refinement of the out-of-hours items is needed.

Managing patient deterioration: evaluation of what works.

Background: Rapid Response Systems (RRS) have been implemented nationally and internationally to improve patient safety in hospital. However, to date the majority of the RRS research evidence has focused on measuring the effectiveness of the intervention on patient outcomes. To evaluate RRS it has been recommended that a multimodal approach is required to address the broad range of process and outcome measures required to determine the effectiveness of the RRS concept. Aim: The aim of this paper is to evaluate the official RRS programme theoretical assumptions regarding how the programme is meant to work against actual practice in order to determine what works. Methods: The research design was a multiple case study approach of four wards in two hospitals in Northern Ireland. It followed the principles of realist evaluation research which allowed empirical data to be gathered to test and refine RRS programme theory [1]. This approach used a variety of mixed methods to test the programme theories including individual and focus group interviews with a purposive sample of 75 nurses and doctors, observation of ward practices and documentary analysis. The findings from the case studies were analysed and compared within and across cases to identify what works for whom and in what circumstances. Results: The RRS programme theories were critically evaluated and compared with study findings to develop a mid-range theory to explain what works, for whom in what circumstances. The findings of what works suggests that clinical experience, established working relationships, flexible implementation of protocols, ongoing experiential learning, empowerment and pre-emptive management are key to the success of RRS implementation.  Conclusion:These findings highlight the combination of factors that can improve the implementation of RRS and in light of this evidence several recommendations are made to provide policymakers with guidance and direction for their success and sustainability.References: 1.Pawson R and Tilley N. (1997) Realistic Evaluation. Sage Publications; LondonType of submission: Concurrent session Source of funding: Sandra Ryan Fellowship funded by the School of Nursing & Midwifery, Queen’s University of Belfast

Identification of novel Factor XI mutations in a patient requiring dental extractions

Factor XI is a serine protease that participates in the intrinsic pathway of blood coagulation. Patients deficient in factor XI exhibit varying degrees of post operative bleeding following invasive surgical procedures such as dental extractions. Objectives: The aim of the study was to identify the specific mutations in a patient from a family with known factor XI deficiency. Methods: Samples were obtained from the patient, his mother and his father and subjected to DNA sequencing. Each protein coding exon 2-15 of the factor XI gene was amplified by polymerase chain reaction (PCR) followed by bidirectional sequencing utilizing di-deoxy chain termination chemistry. Results: The patient had a factor XI level of 20% of normal. Initial sequencing of factor XI from the patient identified a point mutation (646G>A) and a putative splice site mutation (1567+4A>T) in intron 13. These are novel previously unreported mutations. DNA sequence analysis of the mother revealed the 1567+4A>T mutation and the father exhibited the 646G>A mutation. As a consequence the treatment proceeded without serious bleeding complication and required administration only of transexamic acid though factor XI was available as haemostatic cover. Conclusion: The two mutations identified in this family are novel; further laboratory investigation of the functional consequences of those mutations is currently underway. Although factor XI deficiency is rare in the Northern Irish population this study highlights the techniques available to sequence and analyse this and similar haematological disorders.