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Dr Nadine Upton, Post-doctoral Scientist | Curation made possible by Deep Science Ventures


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Microfluidic-Based Bacteria Isolation from Whole Blood for Diagnostics of Blood Stream Infection.

Abstract: Bacterial blood stream infection (BSI) potentially leads to life-threatening clinical conditions and medical emergencies such as severe sepsis, septic shock, and multi organ failure syndrome. Blood culturing is currently the gold standard for the identification of microorganisms and, although it has been automated over the decade, the process still requires 24-72 h to complete. This long turnaround time, especially for the identification of antimicrobial resistance, is driving the development of rapid molecular diagnostic methods. Rapid detection of microbial pathogens in blood related to bloodstream infections will allow the clinician to decide on or adjust the antimicrobial therapy potentially reducing the morbidity, mortality, and economic burden associated with BSI. For molecular-based methods, there is a lot to gain from an improved and straightforward method for isolation of bacteria from whole blood for downstream processing.We describe a microfluidic-based sample-preparation approach that rapidly and selectively lyses all blood cells while it extracts intact bacteria for downstream analysis. Whole blood is exposed to a mild detergent, which lyses most blood cells, and then to osmotic shock using deionized water, which eliminates the remaining white blood cells. The recovered bacteria are 100 % viable, which opens up possibilities for performing drug susceptibility tests and for nucleic-acid-based molecular identification.

Pub.: 04 Jan '17, Pinned: 24 Feb '17

Deficits in knowledge, attitude, and practice towards blood culture sampling: results of a nationwide mixed-methods study among inpatient care physicians in Germany.

Abstract: Blood culture (BC) sampling rates in Germany are considerably lower than recommended. Aim of our study was to assess knowledge, attitudes, and practice of physicians in Germany regarding BC diagnostics.We conducted a cross-sectional mixed-methods study among physicians working in inpatient care in Germany. Based on the results of qualitative focus groups, a questionnaire-based quantitative study was conducted in 2015-2016. In total, 706 medical doctors and final-year medical students from 11 out of 16 federal states in Germany participated.BC sampling was considered an important diagnostic tool by 95% of the participants. However, only 23% of them would collect BCs in three scenarios for which BC ordering is recommended by present guidelines in Germany; almost one out of ten physicians would not have taken blood cultures in any of the three scenarios. The majority of participants (74%) reported not to adhere to the guideline recommendation that blood culture sampling should include at least two blood culture sets from two different injection sites. High routine in blood culture sampling, perceived importance of blood culture diagnostics, the availability of an in-house microbiological lab, and the department the physician worked in were identified as predictors for good blood culture practice.Our study suggests that there are substantial deficits in BC ordering and the application of guidelines for good BC practice in Germany. Based on these findings, multimodal interventions appear necessary for improving BC diagnostics.

Pub.: 17 Feb '17, Pinned: 24 Feb '17

Digital health system for personalised COPD long-term management.

Abstract: Recent telehealth studies have demonstrated minor impact on patients affected by long-term conditions. The use of technology does not guarantee the compliance required for sustained collection of high-quality symptom and physiological data. Remote monitoring alone is not sufficient for successful disease management. A patient-centred design approach is needed in order to allow the personalisation of interventions and encourage the completion of daily self-management tasks.A digital health system was designed to support patients suffering from chronic obstructive pulmonary disease in self-managing their condition. The system includes a mobile application running on a consumer tablet personal computer and a secure backend server accessible to the health professionals in charge of patient management. The patient daily routine included the completion of an adaptive, electronic symptom diary on the tablet, and the measurement of oxygen saturation via a wireless pulse oximeter.The design of the system was based on a patient-centred design approach, informed by patient workshops. One hundred and ten patients in the intervention arm of a randomised controlled trial were subsequently given the tablet computer and pulse oximeter for a 12-month period. Patients were encouraged, but not mandated, to use the digital health system daily. The average used was 6.0 times a week by all those who participated in the full trial. Three months after enrolment, patients were able to complete their symptom diary and oxygen saturation measurement in less than 1 m 40s (96% of symptom diaries). Custom algorithms, based on the self-monitoring data collected during the first 50 days of use, were developed to personalise alert thresholds.Strategies and tools aimed at refining a digital health intervention require iterative use to enable convergence on an optimal, usable design. 'Continuous improvement' allowed feedback from users to have an immediate impact on the design of the system (e.g., collection of quality data), resulting in high compliance with self-monitoring over a prolonged period of time (12-month). Health professionals were prompted by prioritisation algorithms to review patient data, which led to their regular use of the remote monitoring website throughout the trial.Trial registration: ISRCTN40367841 . Registered 17/10/2012.

Pub.: 22 Feb '17, Pinned: 24 Feb '17

Automated Blood Sample Preparation Unit (ABSPU) for Portable Microfluidic Flow Cytometry.

Abstract: Portable microfluidic diagnostic devices, including flow cytometers, are being developed for point-of-care settings, especially in conjunction with inexpensive imaging devices such as mobile phone cameras. However, two pervasive drawbacks of these have been the lack of automated sample preparation processes and cells settling out of sample suspensions, leading to inaccurate results. We report an automated blood sample preparation unit (ABSPU) to prevent blood samples from settling in a reservoir during loading of samples in flow cytometers. This apparatus automates the preanalytical steps of dilution and staining of blood cells prior to microfluidic loading. It employs an assembly with a miniature vibration motor to drive turbulence in a sample reservoir. To validate performance of this system, we present experimental evidence demonstrating prevention of blood cell settling, cell integrity, and staining of cells prior to flow cytometric analysis. This setup is further integrated with a microfluidic imaging flow cytometer to investigate cell count variability. With no need for prior sample preparation, a drop of whole blood can be directly introduced to the setup without premixing with buffers manually. Our results show that integration of this assembly with microfluidic analysis provides a competent automation tool for low-cost point-of-care blood-based diagnostics.

Pub.: 26 Aug '16, Pinned: 21 Feb '17

Towards personalised management of atherosclerosis via computational models in vascular clinics: technology based on patient-specific simulation approach.

Abstract: The development of a new technology based on patient-specific modelling for personalised healthcare in the case of atherosclerosis is presented. Atherosclerosis is the main cause of death in the world and it has become a burden on clinical services as it manifests itself in many diverse forms, such as coronary artery disease, cerebrovascular disease/stroke and peripheral arterial disease. It is also a multifactorial, chronic and systemic process that lasts for a lifetime, putting enormous financial and clinical pressure on national health systems. In this Letter, the postulate is that the development of new technologies for healthcare using computer simulations can, in the future, be developed as in-silico management and support systems. These new technologies will be based on predictive models (including the integration of observations, theories and predictions across a range of temporal and spatial scales, scientific disciplines, key risk factors and anatomical sub-systems) combined with digital patient data and visualisation tools. Although the problem is extremely complex, a simulation workflow and an exemplar application of this type of technology for clinical use is presented, which is currently being developed by a multidisciplinary team following the requirements and constraints of the Vascular Service Unit at the University College Hospital, London.

Pub.: 01 Jan '14, Pinned: 21 Feb '17

Towards personal health care with model-guided medicine: long-term PPPM-related strategies and realisation opportunities within 'Horizon 2020'.

Abstract: At the international EPMA Summit carried out in the EU Parliament (September 2013), the main challenges in Predictive, Preventive and Personalised Medicine have been discussed and strategies outlined in order to implement scientific and technological innovation in medicine and healthcare utilising new strategic programmes such as 'Horizon 2020'. The joint EPMA (European Association for Predictive, Preventive and Personalised Medicine) / IFCARS (International Foundation for Computer Assisted Radiology and Surgery) paper emphasises the consolidate position of the leading experts who are aware of the great responsibility of being on a forefront of predictive, preventive and personalised medicine. Both societies consider long-term international partnerships and multidisciplinary projects to create PPPM relevant innovation in science, technological tools and practical implementation in healthcare. Personalisation in healthcare urgently needs innovation in design of PPPM-related medical services, new products, research, education, didactic materials, propagation of targeted prevention in the society and treatments tailored to the person. For the paradigm shift from delayed reactive to predictive, preventive and personalised medicine, a new culture should be created in communication between individual professional domains, between doctor and patient, as well as in communication with individual social (sub)groups and patient cohorts. This is a long-term mission in personalised healthcare with the whole spectrum of instruments available and to be created in the field.

Pub.: 03 Jun '14, Pinned: 21 Feb '17

Other side of the coin for personalised medicine and healthcare: content analysis of 'personalised' practices in the literature.

Abstract: Various terms and definitions are used to describe personalised approaches to medicine and healthcare, but in ambiguous and inconsistent ways. They mostly have been defined in a top-down manner. However, actual practices might take different paths. Here, we aimed to provide a 'practice-based' perspective on the debate by analysing the content of 'personalised' practices published in the literature.The search in PubMed and EMBASE (April 2014) using the terms frequently used for personalised approaches resulted in 5333 records. 2 independent researchers used different strategies for screening, resulting in 157 articles describing 88 'personalised' practices that were implemented/presented on at least 1 individual/patient case. The content analysis was grounded on these data and did not have a priori analytical frameworks.'Personalised medicine/healthcare' can be a commodity in the healthcare market, a way how health services are provided, or a keyword for emerging applications. It can help individuals/patients to gain control of their health, health professionals to provide better services, healthcare organisations to increase effectiveness and efficiency, or national health systems to increase performance. Country examples indicated that for integration of practices into health services, attitude towards innovations and health system and policy context is important. Categorisation based on the terms or the technologies used, if any, was not possible.This study is the first to provide a comprehensive content analysis of the 'personalised' practices in the literature. Unlike the top-down definitions, our findings highlighted not the technologies but real-life issues faced by the practices. 'Personalised medicine' and 'personalised healthcare' can be differentiated by using the former for specific tools available and the latter for health services with a holistic approach, implemented in certain contexts. To realise integration of 'personalised medicine/healthcare' into real life, science, technology, health policy and practice, and society domains must work together.

Pub.: 15 Jul '16, Pinned: 21 Feb '17

Performance analysis of a machine learning flagging system used to identify a group of individuals at a high risk for colorectal cancer.

Abstract: Individuals with colorectal cancer (CRC) have a tendency to intestinal bleeding which may result in mild to severe iron deficiency anemia, but for many colon cancer patients hematological abnormalities are subtle. The fecal occult blood test (FOBT) is used as a pre-screening test whereby those with a positive FOBT are referred to colonscopy. We sought to determine if information contained in the complete blood count (CBC) report coud be processed automatically and used to predict the presence of occult colorectal cancer (CRC) in the setting of a large health services plan. Using the health records of the Maccabi Health Services (MHS) we reviewed CBC reports for 112,584 study subjects of whom 133 were diagnosed with CRC in 2008 and analysed these with the MeScore tool. The odds ratio for being diagnosed with CRC in 2008 was calculated with regards to the MeScore, using cutoff levels of 97% and 99% percentiles. For individuals in the highest one percentile, the odds ratio for CRC was 21.8 (95% CI 13.8 to 34.2). For the majority of the individuals with cancer, CRC was not suspected at the time of the blood draw. Frequent use of anticoagulants, the presence of other gastrointestinal pathologies and non-GI malignancies were assocaitged with false positive MeScores. The MeScore can help identify individuals in the population who would benefit most from CRC screening, including those with no clinical signs or symptoms of CRC.

Pub.: 10 Feb '17, Pinned: 21 Feb '17