Utilization of BPM+ Health for the Representation of Clinical Knowledge: A Framework for the Expression and Assessment of Clinical Practice Guidelines (CPG) Utilizing Existing and Emerging Object Management Group (OMG) Standards.

Clinical Practice Guidelines (CPG), meant to express best practices in healthcare, are commonly presented as narrative documents communicating care processes, decision making, and clinical case knowledge. However, these narratives in and of themselves lack the specificity and conciseness in their use of language to unambiguously express quality clinical recommendations. This impacts the confidence of clinicians, uptake, and implementation of the guidance. As important as the quality of the clinical knowledge articulated, is the quality of the language(s) and methods used to express the recommendations. In this paper, we propose the BPM+ family of modeling languages as a potential solution to this challenge. We present a formalized process and framework for translating CPGs into a standardized BPM+ model. Further, we discuss the features and characteristics of modeling languages that underpin the quality in expressing clinical recommendations. Using an existing CPG, we defined a systematic series of steps to deconstruct the CPG into knowledge constituents, assign CPG knowledge constituents to BPM+ elements, and re-assemble the parts into a clear, precise, and executable model. Limitations of both the CPG and the current BPM+ languages are discussed.

Incurred sample reanalysis at GSK: what have we learned?

Outcomes of incurred sample reanalysis (ISR) studies have been reviewed from a decade of internally supported bioanalysis. From over 1000 bioanalytical pharmacokinetic end points, 26 bioanalytical studies have failed against predefined ISR acceptance criteria, ultimately resulting in the rejection of three partial and two full datasets (instability or preanalytic contamination). The remaining investigations highlighted methodological root causes including unexpected within-study assay variability, inappropriate assay range and sample homogeneity. However, the data variability remained acceptable for the purposes of decision-making and asset progression. Overall, ISR adds value in early development to characterize the reliability of a nascent assay and then also at the latter stages where pharmacokinetic data are pivotal to submission. However, for the intermediate development studies there is a question whether ISR adds much additional value in understanding assay performance or whether the industry is just too conservative to follow the guidance. This is where the future debate must be.

A dual-spectrometer approach to reflectance measurements under sub-optimal sky conditions.

This paper presents a practical method for the development of spectral reflectance libraries under sub-optimal sky conditions. Although there are commercially available spectrometers which simultaneously measure both downwelling and upwelling radiance to mitigate the impact of sub-optimal sky conditions, these spectrometers only record in the visible and near infra-red. There are presently no commercially available spectrometers with this capability that can record the visible through short-wave infra-red. This paper presents a practical method of recording and processing data using coordinated measurements from two full-range spectrometers and discusses potential pitfalls and solutions required to achieve accurate reflectance spectra. Results demonstrate that high-quality spectral reflectance libraries can be developed with this approach.

Incurred sample reproducibility: views and recommendations by the European Bioanalysis Forum.

Following intensive discussions, review, alignment of procedures and multiple surveys among their member companies, the European Bioanalysis Forum (EBF) is providing a recommendation on how to integrate incurred sample reproducibility (ISR) in the bioanalytical process. The recommendation aims to provide guidance throughout the lifecycle of a validated method, including the application of the method in study support. In its recommendation, the EBF considers both the internal discussions with EBF member companies, as well as the input provided in international meetings where ISR was discussed. The ultimate goal of the EBF recommendation is to ensure that bioanalytical methods can provide accurate and reproducible concentration data for pharmacokinetic and/or toxicokinetic evaluation, without any compromise, while safeguarding the optimal use of laboratory resources.

Evaluation of ultra-performance liquid chromatography in the bioanalysis of small molecule drug candidates in plasma.

Ultra-performance liquid chromatography (UPLC) combined with mass spectrometric detection (MS) is used successfully in the bioanalysis of small molecule drug candidates in plasma. UPLC-MS is shown to increase sample throughput by reducing run times over 3-fold, without compromising analytical sensitivity or analyte resolution. The technique is demonstrated to be practical and robust on a commercially available ultra-high pressure system when injecting extracts of plasma and has also shown to be a technique that can be used effectively on a conventional high-performance liquid chromatography system fitted with short columns (

Isolated Roux-loop pancreaticojejunostomy: a series of 61 patients with zero postoperative pancreaticoenteric leaks.

There have been approximately 70 reported variations of reconstruction after pancreaticoduodenectomy (PD). The pancreaticojejunal (PJ) anastomosis is the source of most reported morbidity and mortality. In this study, we aimed to identify the anastomotic leak rate in patients undergoing PD for malignant disease using a proximal isolated jejunal pancreatic anastomosis. Sixty-one consecutive patients undergoing PD (26 women and 35 men; age range, 41-79 years, mean age, 62 years). had an identical reconstruction. The PJ anastomosis was performed using the most proximal isolated jejunum in two layers: interrupted 4.0 Prolene was used to achieve mucosal/ductal continuity, and 3.0 Prolene was used for the serosal/parenchymal anastomosis, around an appropriately sized stent. All postoperative complications were recorded. A pancreatic leak was defined as persistent discharge of amylase-rich pancreatic drain fluid. The overall complication rate was 44% (27 of 61, including 15 chest infections, 8 wound infections, and 2 postoperative cardiac arrhythmias). There were 3 deaths (30-day mortality rate, 5%). One patient died after a cerebrovascular accident, one from respiratory failure secondary to pneumonia, and the third of methicillin-resistant Staphylococcus aureus septicemia after small bowel ischemia caused by pressure necrosis from a drain. There were no PJ anastomotic leaks. This method of pancreatojejunostomy has produced a 0% leak rate in this center.