Histological confirmation of breast cancer registration and self-reporting in England and Wales: a cohort study within the UK Collaborative Trial of Ovarian Cancer Screening

In research studies, accurate information of cancer diagnosis is crucial. In women with breast cancer (BC), we compare cancer registration (CR) in England/Wales and self-reporting with independent confirmation

Designing a package of sexual and reproductive health and HIV outreach services to meet the heterogeneous preferences of young people in Malawi: results from a discrete choice experiment.

BACKGROUND: This article examines young people's preferences for integrated family planning (FP) and HIV services in rural Malawi. Different hypothetical configurations for outreach services are presented using a Discrete Choice Experiment (DCE). Responses are analysed using Random Parameters Logit and Generalised Mixed Logit (GMXL) models in preference space and a GMXL model parameterised in willingness-to-pay space. Simulations are used to estimate the proportion of respondents expected to choose different service packages as elements are varied individually and in combination. RESULTS: Responses were collected from 537 young people aged 15-24. Results show that when considering attending an outreach service to access family planning young people value confidentiality and the availability of HIV services including HIV counselling and testing (HCT) and HIV treatment, though significant observable and unobservable heterogeneity is present. Female respondents and those aged 20-24 were less concerned with service confidentiality compared to male respondents and those aged 15-19; respondents who were in a relationship at the time of the survey valued confidentiality more than those who reported being single. The addition of sports and recreation for young people may also be an attractive feature of a youth-friendly service; however, preferences for this attribute vary according to respondent gender. Results of the simulation modelling indicate that the most preferred service package is one that offers confidential services, both HCT and HIV treatment and sports for youth, with up to 32% of respondents expected to choose this service over a service where clients may have concerns over confidentiality, only HCT is available and there are no additional activities for young people. Estimates of willingness-to-pay for service attributes indicate that respondents were willing to pay up to USD$1.76 for confidentiality, USD$0.65 for a service offering both HCT and HIV treatment and USD$0.26 for a service including sports for youth. CONCLUSIONS: Young people were able to complete a complex DCE and appeared to trade between the different characteristics used to describe the outreach services. These findings may offer important insight to policy makers designing youth friendly SRH outreach services and providers aiming to improve the acceptability and uptake of FP services

Elevation of TP53 Autoantibody Prior to CA125 in Preclinical Invasive Epithelial Ovarian Cancer

Purpose: The TP53 tumor suppressor gene is mutated in >95% of high grade serous ovarian cancers. Detecting an autologous antibody response to TP53 might improve early detection. Experimental design: An immunoassay was developed to measure TP53 autoantibody in sera from 378 cases of invasive epithelial ovarian cancer and in 944 age-matched healthy controls from the United States, Australia and the United Kingdom. Serial preclinical samples from cases and controls were also assayed from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Results: Using a cut-off of 78 U/mL to achieve a specificity of 97.4%, TP53 autoantibody were elevated in 30% of 50 cases from MD Anderson, 21.3% of 108 cases from the Australian Ovarian Cancer Study and 21% of 220 cases from the UKCTOCS. Among 164 cases with rising CA125 detected with the UKCTOCS risk of ovarian cancer algorithm (ROCA), 20.7% had elevated TP53 autoantibody. In cases missed by the ROCA, 16% of cases had elevated TP53 autoantibody. Of the 34 ovarian cancer cases detected with the ROCA, TP53 autoantibody titers were elevated 11.0 months prior to CA125. In the 9 cases missed by the ROCA, TP53 autoantibody was elevated 22.9 months before cancer diagnosis. Similar sensitivity was obtained using assays with specific mutant and wild-type TP53. Conclusion: TP53 autoantibody levels provide a biomarker with clinically significant lead time over elevation of CA125 or an elevated ROCA value. Quantitative assessment of autoantibodies in combination with CA125 hold promise for earlier detection of invasive epithelial ovarian cancer

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Perioperative fluid and volume management: physiological basis, tools and strategies

Fluid and volume therapy is an important cornerstone of treating critically ill patients in the intensive care unit and in the operating room. New findings concerning the vascular barrier, its physiological functions, and its role regarding vascular leakage have lead to a new view of fluid and volume administration. Avoiding hypervolemia, as well as hypovolemia, plays a pivotal role when treating patients both perioperatively and in the intensive care unit. The various studies comparing restrictive vs. liberal fluid and volume management are not directly comparable, do not differ (in most instances) between colloid and crystalloid administration, and mostly do not refer to the vascular barrier's physiologic basis. In addition, very few studies have analyzed the use of advanced hemodynamic monitoring for volume management

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

GEICO (Spanish Group for Investigation on Ovarian Cancer) treatment guidelines in ovarian cancer 2012

In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GEICO), the first “Treatment Guidelines in Ovarian Cancer” were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308–316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750–755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies.

Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer