Data-driven digital health technologies in the remote clinical care of diabetic foot ulcers: a scoping review.

Background: The availability and effectiveness of Digital Health Technologies (DHTs) to support clinicians, empower patients, and generate economic savings for national healthcare systems are growing rapidly. Of particular promise is the capacity of DHTs to autonomously facilitate remote monitoring and treatment. Diabetic Foot Ulcers (DFUs) are characterised by high rates of infection, amputation, mortality, and healthcare costs. With clinical outcomes contingent on activities that can be readily monitored, DFUs present a promising focus for the application of remote DHTs. Objective: This scoping review has been conducted as a first step toward ascertaining fthe data-related challenges and opportunities for the development of more comprehensive, integrated, and individualised sense/act DHTs. We review the latest developments in the application of DHTs to the remote care of DFUs. We cover the types of DHTs in development and their features, technological readiness, and scope of clinical testing. Eligibility criteria: Only peer-reviewed original experimental and observational studies, case series and qualitative studies were included in literature searches. All reviews and manuscripts presenting pre-trial prototype technologies were excluded. Methods: An initial search of three databases (Web of Science, MEDLINE, and Scopus) generated 1,925 English-language papers for screening. 388 papers were assessed as eligible for full-text screening by the review team. 81 manuscripts were found to meet the eligibility criteria. Results: Only 19% of studies incorporated multiple DHTs. We categorised 56% of studies as 'Treatment-Manual', i.e. studies involving technologies aimed at treatment requiring manual data generation, and 26% as 'Prevention-Autonomous', i.e. studies of technologies generating data autonomously through wearable sensors aimed at ulcer prevention through patient behavioural change. Only 10% of studies involved more ambitious 'Treatment-Autonomous' interventions. We found that studies generally reported high levels of patient adherence and satisfaction. Conclusions: Our findings point to a major potential role for DHTs in remote personalised medical management of DFUs. However, larger studies are required to assess their impact. Here, we see opportunities for developing much larger, more comprehensive, and integrated monitoring and decision support systems with the potential to address the disease in a more complete context by capturing and integrating data from multiple sources from subjective and objective measurements.

An innovative non-invasive technique for subcutaneous tumour measurements.

INTRODUCTION: In oncological drug development, animal studies continue to play a central role in which the volume of subcutaneous tumours is monitored to assess the efficacy of new drugs. The tumour volume is estimated by taking the volume to be that of a regular spheroid with the same dimensions. However, this method is subjective, insufficiently traceable, and is subject to error in the accuracy of volume estimates as tumours are frequently irregular. METHODS & RESULTS: This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. Additionally, we explore the impact of six different tumour morphologies on volume estimation and the detection of treatment effects using a computational tumour growth model. Finally, we propose an alternative method to callipers for estimating volume-BioVolumeTM, a 3D scanning technique. BioVolume simultaneously captures both stereo RGB (Red, Green and Blue) images from different light sources and infrared thermal images of the tumour in under a second. It then detects the tumour region automatically and estimates the tumour volume in under a minute. Furthermore, images can be processed in parallel within the cloud and so the time required to process multiple images is similar to that required for a single image. We present data of a pre-production unit test consisting of 297 scans from over 120 mice collected by four different operators. CONCLUSION: This work demonstrates that it is possible to record tumour measurements in a rapid minimally invasive, morphology-independent way, and with less human-bias compared to callipers, whilst also improving data traceability. Furthermore, the images collected by BioVolume may be useful, for example, as a source of biomarkers for animal welfare and secondary drug toxicity / efficacy.

Non-locking screw insertion: No benefit seen if tightness exceeds 80% of the maximum torque.

BACKGROUND: Millions of non-locking screws are manually tightened during surgery each year, but their insertion frequently results in overtightening and damage to the surrounding bone. We postulated that by calculating the torque limit of a screw hole, using bone and screw properties, the risk of overtightening during screw insertion could be reduced. Additionally, predicted maximum torque could be used to identify optimum screw torque, as a percentage of the maximum, based on applied compression and residual pullout strength. METHODS: Longitudinal cross-sections were taken from juvenile bovine tibial diaphyses, a validated surrogate of human bone, and 3.5 mm cortical non-locking screws were inserted. Fifty-four samples were used to define the association between stripping torque and cortical thickness. The relationship derived enabled prediction of insertion torques representing 40 to 100% of the theoretical stripping torque (Tstr) for a further 170 samples. Screw-bone compression generated during insertion was measured, followed immediately by axial pullout testing. FINDINGS: Screw-bone compression increased linearly with applied torque up to 80% of Tstr (R2 = 0.752, p < 0.001), but beyond this, no significant further compression was generated. After screw insertion, with all screw threads engaged, more tightening did not create any significant (R2 = 0.000, p = 0.498) increase in pullout strength. INTERPRETATION: Increasing screw tightness beyond 80% of the maximum did not increase screw-bone compression. Variations in torques below Tstr, did not affect pullout forces of inserted screws. Further validation of these findings in human bone and creation of clinical guidelines based on this research approach should improve surgical outcomes and reduce operative costs.

Introducing an automated high content confocal imaging approach for Organs-on-Chips.

Organ-Chips are micro-engineered systems that aim to recapitulate the organ microenvironment. Implementation of Organ-Chips within the pharmaceutical industry aims to improve the probability of success of drugs reaching late stage clinical trial by generating models for drug discovery that are of human origin and have disease relevance. We are adopting the use of Organ-Chips for enhancing pre-clinical efficacy and toxicity evaluation and prediction. Whilst capturing cellular phenotype via imaging in response to drug exposure is a useful readout in these models, application has been limited due to difficulties in imaging the chips at scale. Here we created an end-to-end, automated workflow to capture and analyse confocal images of multicellular Organ-Chips to assess detailed cellular phenotype across large batches of chips. By automating this process, we not only reduced acquisition time, but we also minimised process variability and user bias. This enabled us to establish, for the first time, a framework of statistical best practice for Organ-Chip imaging, creating the capability of using Organ-Chips and imaging for routine testing in drug discovery applications that rely on quantitative image data for decision making. We tested our approach using benzbromarone, whose mechanism of toxicity has been linked to mitochondrial damage with subsequent induction of apoptosis and necrosis, and staurosporine, a tool inducer of apoptosis. We also applied this workflow to assess the hepatotoxic effect of an active AstraZeneca drug candidate illustrating its applicability in drug safety assessment beyond testing tool compounds. Finally, we have demonstrated that this approach could be adapted to Organ-Chips of different shapes and sizes through application to a Kidney-Chip.