Philip Pemberton’s research while affiliated with University of Toronto and other places

Monitoring systems have wide clinical application in health service provisions, for example, in rehabilitation, pre- and post-surgical assessment, monitoring of the acute medical patient and management of chronic conditions [1-3]. They also provide new opportunities for insights into the workplace activities, processes and stressors of clinical staff and health workers [4]. In prior work of The Quantified Outpatient Project, a prototype 24-hour wearable and ambient monitoring system was developed, and opportunities and challenges identified [1]. A new “Sense247” wearable and ambient monitoring system is now presented. The underpinning vision is for a generic and expandable “core” sensing system to provide objective sensed recordings that are combined with quantified subjective reports, with the potential for beneficial insights for both patients and health workers.

Wearable multi-modal monitoring systems, capable of robust real-world recording during the activities of daily life, have the potential to provide rich objective experiential and well-being accounts. Such sensing systems have wide clinical application in rehabilitation, in pre- and post-surgical assessment, in monitoring of the acute medical patient and in management of chronic conditions among others. They can also provide new opportunities for insights into workplace activities, processes and stressors of clinical staff and health workers. In prior work of The Quantified Outpatient Project (http://quantifiedoutpatient.com), a prototype 24-hr wearable and ambient recording system was developed and tested with clinicians and healthy participants. The underpinning vision is for a generic and expandable “core” sensing system to provide objective sensed recordings that supplement, not supplant, subjective reports. To this end, continuously-sensed physiological, environmental and actigraphy recordings are combined with quantified subjective reports. A clinical prototyping methodology, with clinician and healthy user participation, was employed to evolve the new Sense247 design. This new design benefits from re-positioned sensors, long-life USB rechargeable batteries, and upgraded data logging units that are smaller and lighter than a typical smartphone, and approximately half the size of the original prototype units. These improvements have beneficial impacts in terms of wearability, usability and system performance outcomes. Whilst there are challenges in achieving robust, secure, ambulatory, multi-modal recordings from user-applied, hygienically-compliant systems, these challenges are not insurmountable, and the potential benefits are considerable, both in terms of improved insights and improved outcomes.

1. Introduction Patient monitoring systems capable of accurate recording in the real-world, during the activities of everyday living, can provide rich objective accounts of patient well-being that have broad application in clinical decision support. Combining physiological, environmental and actigraphy sensing together with a quantified subjective patient report and activity log, provides new opportunities and new challenges in big data analysis, data mining and visual analytics. 2. Method An iterative prototyping approach together with clinical collaboration informed the design and development of a novel 24hr sensing system with broad application relevant to sleep assessment. The system design, sensor selection and visual analytic strategies were informed by literature review and pilot studies with i) clinical staff and ii) healthy participants. The sensing system comprised, i) a daytime wearable sensing unit (on-body accelerometry for Metabolic Equivalent Task, pulse, skin temperature and resistivity) and ii) two night-time sensing units (an on-body unit as per daytime but with wrist accelerometry, and a bedside unit for ambient light, temperature and sound-level). Continuous recordings were used to generate averages, minima and maxima in 1-minute, 15-minute, 1-hour and 4-hour intervals. For data mining and visual analytics, these records were combined with quantified accounts of subjective user reports and activity logs. Ten subjects (including three clinicians) tested the system for up to three consecutive days and nights and provided assessments of use and comfortability. Five clinicians were interviewed regarding system applications, barriers to use, data use and visual analytics. 3. Results Data acquisition was successful across a wide range of MET levels. System comfortability was good but with some discomfort and skin irritation arising from prolonged use of a carotid pulse sensor (selected for its robust performance compared with wristband alternatives). Electrooculography sensing for REM sleep detection was attempted but was uncomfortable and performance was unsatisfactory. Usability of the system benefitted from prolonged battery operation. Few data losses resulted from user-administration of sensors, but more resulted from a lack of prototype ruggedisation. Attempts at intuitive multivariate data visualizations, including heat maps, motion charts and clustered views, had limited success. However, the system and approach was assessed as very good for real-life application and decision support. 4. Discussion 24hr outpatient sensing has wide clinical application in rehabilitation, in the management of chronic conditions and, in pre- and post-surgical assessment. However, better detection of both low level activity and sleep is required than currently available in commercial activity monitoring devices. 5. Conclusion Multi-modal outpatient monitoring can perform robustly and with acceptable comfortability across a spectrum of activity types and levels, however, system robustness and ease-of-use are paramount to reliability, and users’ self-application of sensors requires careful attention. The new big un-delineated, multi-modal, multi-dimensional, data spaces created are unfamiliar, uncharted territories that require new understandings, guidance and training. Data mining and visual analytics provide new research insights but there are many challenges regarding their translation into clinical practice.

Objectives: We hypothesized that intensivists unfamiliar with an ICU team and the context of that ICU would affect patient outcomes. We examined differences in mortality when ICU patients were admitted under intensivists routinely working in that ICU and compared with those admitted by intensivists familiar with an ICU elsewhere in the same hospital. Design, settings, and patients: A 5-year natural experimental crossover study involving patients admitted to four ICUs in a large U.K. teaching hospital. Interventions: During a period of service reconfiguration, intensivists routinely rostered to work in one ICU worked in another of the hospital's four ICUs. "Home" intensivists were those who continued to work in their usual ICU; "visitor" intensivists were those who delivered care in an unfamiliar ICU. Patient data were obtained from electronic patient records to provide analysis on sex, age, admission Sequential Organ Failure Assessment score, date and time of admission, and admission type (elective, transfer, or unplanned). Measurements and main results: We analyzed 9,981 admissions to four separate ICUs over a 5-year period. In total, 34.5% of patients were admitted by intensivists working in nonfamiliar surroundings. Visitor intensivists admitted patients with similar age and gender distributions but with greater physiologic derangement (mean Sequential Organ Failure Assessment score, 4.1 ± 2.8 vs 3.9 ± 2.8; p < 0.001) than home intensivists. Overall ICU mortality rates were higher in visitor intensivists, albeit not significantly so (11.5% vs 10.2%; p = 0.052). However, when the ICUs were analyzed separately, visitor mortality rates were found to be significantly higher than for home intensivists in two of the four ICUs (p = 0.017, 0.006). A multivariable analysis adjusting for confounding factors and the clustering of consultants revealed that the overall mortality rate was significantly higher for visitors (odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.024). A significant interaction between the ICU and visitor status was also detected (p = 0.046), with the visitor effect remaining significant in the two ICUs identified previously (both p = 0.009). Conclusions: Visitor intensivists in some ICUs were associated with higher mortality. The reasons are unknown but could relate to intensivists' practices, unfamiliarity with the patients, or the interaction with the interprofessional team.

Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol−1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol−1, respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10–44) and 42 (32–58) nmol mol−1.

Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), C3H2ClF5O, is a commonly used inhalation anaesthetic. Using a proton transfer reaction mass spectrometer (PTR-MS) we have detected isoflurane in the breath of patients several weeks following major surgery. That isoflurane is detected in the breath of patients so long after being anaesthetised raises questions about when cognitive function has fully returned to a patient. Temporal profiles of isoflurane concentrations in breath are presented for five patients (F/M 3/2, mean age 50 years, min–max 36–58 years) who had undergone liver transplant surgery. In addition, results from a headspace analysis of isoflurane are presented so that the product ions resulting from the reactions of H3O+ with isoflurane in PTR-MS could be easily identified in the absence of the complex chemical environment of breath. Six product ions were identified. In order of increasing m/z (using the 35Cl isotope where appropriate) these are $\text{CHF}_{2}^{+}$ (m/z 51), CHFCl+ (m/z 67), CF3CHCl+ (m/z 117), C3F4OCl+ (m/z 163), C3H2F4OCl+ (m/z 165), and C3F4OCl+ H2O (m/z 183). No protonated parent was detected. For the headspace study both clean air and CO2 enriched clean air (4% CO2) were used as buffer gases in the drift tube of the PTR-MS. The CO2 enriched air was used to determine if exhaled breath would affect the product ion branching ratios. Importantly no significant differences were observed, and therefore for isoflurane the product ion distributions determined in a normal air mixture can be used for breath analysis. Given that PTR-MS can be operated under different reduced electric fields (E/N), the dependence of the product ion branching percentages for isoflurane on E/N (96–138 Td) are reported.

Beta blockers are some of the most studied drugs in the pharmacopoeia. They are already widely used in medicine for treating hypertension, chronic heart failure, tachyarrhythmias, and tremor. Whilst their use in the immediate perioperative patient has been questioned, the use of esmolol in the patients with established septic shock has been recently reported to have favourable outcomes. In this paper, we review the role of the adrenergic system in sepsis and the evidence for the use of beta stimulation and beta blockers from animal models to critically ill patients.

Background: The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. Aims: To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. Methods: A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. Results: Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. Conclusions: Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed.