Patient-Reported Outcome Measures for Post-mastectomy Breast Reconstruction: A Systematic Review of Development and Measurement Properties.

BACKGROUND: Breast reconstruction (BR) is performed to improve outcomes for patients undergoing mastectomy. A recently developed core outcome set for BR includes six patient-reported outcomes that should be measured and reported in all future studies. It is vital that any instrument used to measure these outcomes as part of a core measurement set be robustly developed and validated so data are reliable and accurate. The aim of this systematic review is to evaluate the development and measurement properties of existing BR patient-reported outcome measures (PROMs) to inform instrument selection for future studies. METHODS: A PRISMA-compliant systematic review of development and validation studies of BR PROMs was conducted to assess their measurement properties. PROMs with adequate content validity were assessed using three steps: (1) the methodological quality of each identified study was assessed using the COSMIN Risk of Bias checklist; (2) criteria were applied for assessing good measurement properties; and (3) evidence was summarized and the quality of evidence assessed using a modified GRADE approach. RESULTS: Fourteen articles reported the development and measurement properties of six PROMs. Of these, only three (BREAST-Q, BRECON-31, and EORTC QLQ-BRECON-23) were considered to have adequate content validity and proceeded to full evaluation. This showed that all three PROMs had been robustly developed and validated and demonstrated adequate quality. CONCLUSIONS: BREAST-Q, BRECON-31, and EORTC QLQ-BRECON-23 have been well-developed and demonstrate adequate measurement properties. Work with key stakeholders is now needed to generate consensus regarding which PROM should be recommended for inclusion in a core measurement set.

A novel strategy to reduce very late HIV diagnosis in high-prevalence areas in South-West England: serious incident audit.

Background: Very late diagnosis of HIV is a serious public health issue. We used serious incident reporting (SIR) to identify and address reasons for late diagnoses across the patient pathway. Methods: Cases of very late HIV diagnosis were reported via SIR in two 6-month batches between 2011 and 2012 in Bournemouth, Poole and Bristol. Case notes were reviewed for missed opportunities for earlier diagnosis using a root-cause analysis tool. Results: A total of 33 patients (aged 30-67 years, 66% male) were diagnosed very late. Although the majority were white British (n = 17), Black African (n = 9) and Eastern European (n = 4) ethnicities were over-represented. Twenty-four (73%) patients had clinical indicator conditions for HIV, 30 (91%) had a risk factor for HIV acquisition, with 13 (39%) having 2 or more (men-who-have-sex-with-men (n = 11), partner HIV positive (n = 11), from high-prevalence area (n = 12)). Actions resulting from SIR included increasing awareness of indicator conditions, HIV education days within primary care, and initiatives to increase testing within hospital specialities. Conclusions: SIR allowed identification of reasons for very late HIV diagnosis and provided an impetus for initiatives to address them. SIR may be part of an effective strategy to prevent late diagnosis of HIV which would have important benefits for individual and population health.

Haplotype uncertainty in association studies.

Inferring haplotypes from genotype data is commonly undertaken in population genetic association studies. Within such studies the importance of accounting for uncertainty in the inference of haplotypes is well recognised. We investigate the effectiveness of correcting for uncertainty using simple methods based on the output provided by the PHASE haplotype inference methodology. In case-control analyses investigating non-Hodgkin lymphoma and haplotypes associated with immune regulation we find little effect of making adjustment for uncertainty in inferred haplotypes. Using simulation we introduce a higher degree of haplotype uncertainty than was present in our study data. The simulation represents two genetic loci, physically close on a chromosome, forming haplotypes. Considering a range of allele frequencies, degrees of linkage between the loci, and frequency of missing genotype data, we detail the characteristics of genetic regions which may be susceptible to the influence of haplotype uncertainty. Within our evaluation we find that bias is avoided by considering haplotype probabilities or using multiple imputation, provided that for each of these methods haplotypes are inferred separately for case and control populations; furthermore using multiple imputation provides the facility to incorporate haplotype uncertainty in the estimation of confidence intervals. We discuss the implications of our findings within the context of the complexity of haplotype inference for larger marker rich regions as would typically be encountered in genetic analyses.

Characterization of the variation between batches of Fast-Flo lactose using low frequency dielectric spectroscopy.

The dielectric response of four batches of lactose has been measured over a frequency range of 10(4) to 10(-2) Hz. The spectra corresponding to three of the batches were identical, while the fourth showed a marked reduction in response. This particular batch has also been reported to exhibit longer disintegration times than the other three when formulated as a tablet. The potential use of dielectric spectroscopy as a means of screening batches of pharmaceutical materials is discussed.