Strategies for Identity Testing of Therapeutic Oligonucleotide Drug Substances and Drug Products.

A risk-based approach for routine identity testing of therapeutic oligonucleotide drug substances and drug products is described. Risk analysis of solid-phase oligonucleotide synthesis indicates that intact mass measurement is a powerful technique for confirming synthesis of the intended oligonucleotide. Further risk assessment suggests that the addition of a second, sequence-sensitive identity test, which relies on a comparison of some property of the sample to a reference standard of proven identity, results in a sufficient test of identity for most oligonucleotide drug substances and products. Alternative strategies for drug product identity testing are presented. The analysis creates a common way to communicate risk and should result in a harmonized approach to identity testing that avoids the unnecessary analytical burden associated with routine de novo sequencing, without compromising quality or patient safety.

Between visit variability of thermal imaging of feet in people attending podiatric clinics with diabetic neuropathy at high risk of developing foot ulcers.

OBJECTIVE: People with diabetic neuropathy who have previously ulcerated are at high risk of re-ulceration. They should regularly attend podiatry clinics for surveillance and routine protective podiatric treatment. It has been suggested that inflammation prior to skin breakdown shows up as a hotspot on a thermal image even in the absence of clinical signs. The aim of this study is to quantify inter-patient and intra-patient thermal variations presented by diabetic feet at high risk of ulceration. APPROACH: Whole foot and spot temperatures were recorded for 96 patients who attended two successive podiatry appointments without ulceration 28 [28, 31] days apart, median [interquartile range]. This was a part of a longer study into whether thermal imaging in clinic can reduce the rate of re-ulceration. MAIN RESULTS: The variation in spot temperature right/left differences for single patients between visits was comparable to the variation observed between patients (0.8 [0.3, 1.5] °C compared with 0.9 [0.4, 1.7] °C). Similarly, whole foot temperature variation for a single patient between visits was comparable to the variation observed between patients (0.6 [0.2, 1.1] °C compared with 0.8 [0.2, 1.3] °C). SIGNIFICANCE: Thresholds which depend on thermal differences from visit to visit are unlikely to have sufficient specificity to effectively target treatment designed to prevent the development of foot ulcers.

Bilateral assessment of body core temperature through axillar, tympanic and inner canthi thermometers in a young population.

There are several sites in which the human body core temperature can be estimated and used to identify febrile states in a threat of pandemic situations at high-populational-traffic places (e.g. airports, ports, universities, schools, public buildings). In these locations, a fast method is required for temperature screening of masses. The most common methods are axillar and tympanic thermometers. However, in addition, measurement of the inner canthi (IC) of the eye with infrared thermal (IRT) imaging has been suggested as a fast mass measurement screening tool. OBJECTIVE: It is the aim of this research to identify the bilateral difference of the available body temperature screening methods with potential use for large-scale fever screening and to verify if such a difference is acceptable. APPROACH: A total of 206 young participants (104 females and 102 males) were recruited, having their temperatures taken with the different methods bilaterally under neutral environmental conditions. The obtained results were statistically processed. MAIN RESULTS: Results established absent reference data for site and method in west European populations. The bilateral differences were minor using the IC of the eye monitored with infrared imaging, which was also proved with the Bland-Altmann limits of agreement. SIGNIFICANCE: Based on the findings of this research, despite all methods being able to estimate body core temperature, it is suggested to use IRT images of the IC of the eye, due to its fast, reliable and reproducible procedure for mass screening. Further research is required to understand the higher bilateral variability in using the traditional thermometer axilla and tympanic membrane assessments, since these are the methods currently used within a clinical setup. The same procedure must be applied to fever cases to establish a decision threshold per method.

Thermal symmetry of healthy feet: a precursor to a thermal study of diabetic feet prior to skin breakdown.

Early identification of areas of inflammation may aid prevention of diabetic foot ulcers. A new bespoke thermal camera system has been developed to thermally image feet at risk. Hotspots (areas at least 2.2 °C hotter than the contralateral site) may indicate areas of inflammation prior to any apparent visual signs. This article describes the thermal pattern and symmetry of 103 healthy pairs of feet. 68% of participants were thermally symmetric at the 33 foot sites measured. 32% of participants had at least one hotspot, but hotspots overall only accounted for 5% of the measurements made. Refinements to the definition of hotspots are proposed when considering feet at risk of ulceration.

Thermal imaging today and its relevance to diabetes.

From the historic and simple assessment of temperature by the clinical thermometer, modern infrared technology has opened up new perspectives, especially in the use of thermal imaging to map body surface temperature with a remote sensing camera. Since the 1960s, there is now a greater understanding of thermal physiology and the relationship between skin temperature and blood perfusion. Furthermore, the examination technique, and the advantages of computer-aided digital imaging has greatly improved the reliability of this technology in medicine. Studies in diabetology have shown the value of this new facility and its relevance to clinical assessment of peripheral perfusion and tissue viability.

Adopting the DICOM standard for medical infrared images.

In recent years there has been a resurgence of interest in the application of infrared thermal imaging in medicine. Yet fairly little effort has been spent towards standardisation of the field and a common communication and exchange format for thermal images. Most other medical areas where digital imaging is employed have subscribed to DICOM (Digital Imaging and Communication in Medicine) as a common standard for storing and retrieving medical imagery. In this paper we investigate how the DICOM standard in its current form can be adopted to store and communicate medical infrared images.

Bone mineral density, calcaneal ultrasound, and bone turnover markers in women with ankylosing spondylitis.

OBJECTIVE: To assess bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA) and calcaneal quantitative ultrasound (QUS) in a cohort of pre- and postmenopausal women with ankylosing spondylitis (AS), and to determine any relationships with markers of bone turnover and disease activity or severity. METHODS: Fifty premenopausal and 16 postmenopausal women with AS were studied. Clinical and radiological status was assessed by the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), and Bath AS Radiology Index (BASRI). BMD of the hip and spine was measured by DEXA, and QUS measured at the heel. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), urinary D-pyridinoline crosslinks (D-PYR), and C-reactive protein (CRP) were assayed. RESULTS: Women with AS (n = 66) had reduced BMD at the hip compared to age and sex matched controls (n = 132). The mean t scores were -1.1 and -2.0, and z scores -0.4 and -0.37, for pre- and postmenopausal women, respectively. Four (6%) had osteoporosis and 34 (52%) had osteopenia according to the WHO definitions. Using a multiple regression model, femoral neck BMD was found to be significantly affected by age, body mass index, and the sacroiliac radiographic score. There were no significant correlations of BMD with disease duration or disease activity. QUS measures did not correlate with DEXA measures of BMD. Women with AS had significantly lower markers of bone formation, OC and BALP, and a trend to higher D-PYR than controls. Serum OC levels correlated negatively with femoral neck BMD, whereas D-PYR correlated with CRP levels. CONCLUSION: Women with AS have reduced hip BMD, 0.39 SD below age and sex matched controls. Bone turnover in women with AS is characterized by low OC and BALP.