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Applied Longitudinal Data Analysis Modeling Change And Event Occurrence

Peripheral biochemical monitoring involves the use of wearable devices for minimally invasive or noninvasive measurement of analytes in biofluids such as interstitial fluid, saliva, tears and sweat. The goal in most cases is to obtain measurements that serve as surrogates for circulating analyte concentrations in blood. Key technological developments to date include continuous glucose monitors, which use an indwelling sensor needle to measure glucose in interstitial fluid, and device-integrated sweat stimulation for continuous access to analytes in sweat. Further development of continuous sensing technologies through new electrochemical sensing modalities will be a major focus of future research. While there has been much investment in wearable technologies to sense analytes, less effort has been directed to understanding the physiology of biofluid secretion. Elucidating the underlying biology is crucial for accelerating technological progress, as the biofluid itself often presents the greatest challenge in terms of sample volumes, secretion rates, filtration, active analyte channels, variable pH and salinity, analyte breakdown and other confounding factors.

Accessing analytes in biofluids for peripheral biochemical monitoring

The purpose of this comprehensive review is to: 1) review the physiology of sweat gland function and mechanisms determining the amount and composition of sweat excreted onto the skin surface; 2) provide an overview of the well-established thermoregulatory functions and adaptive responses of the sweat gland; and 3) discuss the state of evidence for potential non-thermoregulatory roles of sweat in the maintenance and/or perturbation of human health. The role of sweating to eliminate waste products and toxicants seems to be minor compared with other avenues of excretion via the kidneys and gastrointestinal tract; as eccrine glands do not adapt to increase excretion rates either via concentrating sweat or increasing overall sweating rate. Studies suggesting a larger role of sweat glands in clearing waste products or toxicants from the body may be an artifact of methodological issues rather than evidence for selective transport. Furthermore, unlike the renal system, it seems that sweat glands do not conserve water loss or concentrate sweat fluid through vasopressin-mediated water reabsorption. Individuals with high NaCl concentrations in sweat (e.g. cystic fibrosis) have an increased risk of NaCl imbalances during prolonged periods of heavy sweating; however, sweat-induced deficiencies appear to be of minimal risk for trace minerals and vitamins. Additional research is needed to elucidate the potential role of eccrine sweating in skin hydration and microbial defense. Finally, the utility of sweat composition as a biomarker for human physiology is currently limited; as more research is needed to determine potential relations between sweat and blood solute concentrations.

https://www.tandfonline.com/doi/pdf/10.1080/23328940.2019.1632145

Physiology of sweat gland function: The roles of sweating and sweat composition in human health

The rapid growth of research in the areas of chemical and biochemical sensors, lab-on-a-chip, mobile technology, and wearable electronics offers an unprecedented opportunity in the development of mobile and wearable point-of-care testing (POCT) systems for self-testing. Successful implementation of such POCT technologies leads to minimal user intervention during operation to reduce user errors; user-friendly, easy-to-use and simple detection platforms; high diagnostic sensitivity and specificity; immediate clinical assessment; and low manufacturing and consumables costs. In this review, we discuss recent developments in the field of highly integrated mobile and wearable POCT systems. In particular, aspects of sample handling platforms, recognition elements and sensing methods, and new materials for signal transducers and powering devices for integration into mobile or wearable POCT systems will be highlighted. We also summarize current challenges and future prospects for providing personal healthcare with sample-in result-out mobile and wearable POCT.

Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing

Athletes are continually seeking new technologies and therapies to gain a competitive edge to maximize their health and performance. Athletes have gravitated toward the use of wearable sensors to monitor their training and recovery. Wearable technologies currently utilized by sports teams monitor both the internal and external workload of athletes. However, there remains an unmet medical need by the sports community to gain further insight into the internal workload of the athlete to tailor recovery protocols to each athlete. The ability to monitor biomarkers from saliva or sweat in a noninvasive and continuous manner remain the next technological gap for sports medical personnel to tailor hydration and recovery protocols per the athlete. The emergence of flexible and stretchable electronics coupled with the ability to quantify biochemical analytes and physiological parameters have enabled the detection of key markers indicative of performance and stress, as reviewed in this paper.

/pdf/wearable-sensors-for-monitoring-the-physiological-and-2io4lrokkg.pdf

Wearable sensors for monitoring the physiological and biochemical profile of the athlete

Implementation of wearable sweat sensors for continuous measurement of fluid based biomarkers (including electrolytes, metabolites and proteins) is an attractive alternative to common, yet intrusive and invasive, practices such as urine or blood analysis. Recent years have witnessed several key demonstrations of sweat based electrochemical sensing in wearable formats, however, there are still significant challenges and opportunities in this space for clinical acceptance, and thus mass implementation of these devices. For instance, there are inherent challenges in establishing direct correlations between sweat-based and gold-standard plasma-based biomarker concentrations for clinical decision-making. In addition, the wearable sweat monitoring devices themselves may exacerbate these challenges, as they can significantly alter sweat physiology (example, sweat rate and composition). Reported here is the demonstration of a fully integrated, wireless, wearable and flexible sweat sensing device for non-obtrusive and continuous monitoring of electrolytes during moderate to intense exertion as a metric for hydration status. The focus of this work is twofold: 1- design of a conformable fluidics systems to suit conditions of operation for sweat collection (to minimize sensor lag) with rapid removal of sweat from the sensing site (to minimize effects on sweat physiology). 2- integration of Na+ and K+ ion-selective electrodes (ISEs) with flexible microfluidics and low noise small footprint electronics components to enable wireless, wearable sweat monitoring. While this device is specific to electrolyte analysis during intense perspiration, the lessons in microfluidics and overall system design are likely applicable across a broad range of analytes.

A wearable patch for continuous monitoring of sweat electrolytes during exertion

Cortisol has long been recognized as the "stress biomarker" in evaluating stress related disorders. Plasma, urine or saliva are the current source for cortisol analysis. The sampling of these biofluids is either invasive or has reliability problems that could lead to inaccurate results. Sweat has drawn increasing attention as a promising source for non-invasive stress analysis. A sensitive HPLC-MS/MS method was developed for the quantitation of cortisol ((11β)-11,17,21-trihydroxypregn-4-ene-3,20-dione) in human eccrine sweat. At least one unknown isomer that has previously not been reported and could potentially interfere with quantification was separated from cortisol with mixed mode RP HPLC. Detection of cortisol was carried out using atmospheric pressure chemical ionization (APCI) and selected reaction monitoring (SRM) in positive ion mode, using cortisol-9,11,12,12-D4 as internal standard. LOD and LOQ were estimated to be 0.04 ng ml(-1) and 0.1 ng ml(-1), respectively. Linear range of 0.10-25.00 ng ml(-1) was obtained. Intraday precision (2.5%-9.7%) and accuracy (0.5%-2.1%), interday precision (12.3%-18.7%) and accuracy (7.1%-15.1%) were achieved. This method has been successfully applied to the cortisol analysis of human eccrine sweat samples. This is the first demonstration that HPLC-MS/MS can be used for the sensitive and highly specific determination of cortisol in human eccrine sweat in the presence of at least one isomer that has similar hydrophobicity as cortisol. This study demonstrated that human eccrine sweat could be used as a promising source for non-invasive assessment of stress biomarkers such as cortisol and other steroid hormones.

/pdf/quantification-of-cortisol-in-human-eccrine-sweat-by-liquid-4a5ndkjtia.pdf

Quantification of cortisol in human eccrine sweat by liquid chromatography - tandem mass spectrometry.

Objective Individuals with life-threatening illness often engage in some form of spirituality to meet increased needs for meaning and purpose. This study aimed to identify the role of spirituality in persons who had reported positive, life-transforming change in relation to life-threatening cancer or cardiac events, and to connect these roles to palliative and supportive care. Method A purposive sample of 10 cardiac survivors and 9 cancer survivors was recruited. Once the participants had given informed consent and passed screening in relation to life-transforming change and distress, they engaged in a semistructured one-hour qualitative interview on the theme of how their life-transforming change occurred in the context of their life-threatening illness. In the present article, our phenomenological analysis focuses on participants' references to purpose and meaning in their lives, with particular attention to the role and context of participants' spirituality. Results Participants mentioned spirituality, meaning, and purpose in many contexts, including connecting with family and friends, nature, art, music, and sometimes creating a relationship with God. Participants often accessed spirituality by enhancing connections in their own lives: with a higher power, people, their work, or themselves. These enhanced connections gave participants greater meaning and purpose in their lives, and substantially helped participants to adjust to their life-threatening illnesses. Significance of results Understanding the roles and contexts of spirituality among patients with a life-threatening illness allows us to develop better palliative and supportive care plans. Spiritually oriented supportive care may include support groups, yoga, meditation, nature, music, prayer, or referral to spiritual or religious counselors. A quantitative scale is needed to help healthcare clinicians assess the spiritual and coping needs of individuals with life-threatening illness.

Spirituality in the context of life-threatening illness and life-transforming change.

Publisher Summary This chapter discusses how palliative care is being extended to relieve the disease symptoms, side effects, and associated burdens that can beset a patient at many points along the course of an illness. The addition of integrative modalities is helpful in enabling palliative care to be very successfully applied well beyond its historical roots in end-of-life care. It presents a successful demonstration of how the principles and practices of integrative palliative care can outperform palliative care that lacks integrative modalities in terms of both the range of service provided and the degree of patient satisfaction. This chapter also addresses the special challenges facing medical researchers when designing experiments to understand subjective human responses to caring—either from animals, from other humans, or from one's self. The caring stimulus, the variety of situational factors, and the subjective response are all complex, and the research strategy must be designed to capture complex data. Two examples of highly successful research program strategies that made excellent use of both qualitative and quantitative methodologies are described, along with the application of combined methodologies in the current research on psycho-socio-spiritual healing. Finally, this chapter suggests ways in which animal companions and animal-assisted intervention may be incorporated into the practice of palliative care.

Increasing the effectiveness of palliative care through integrative modalities: conceptualizing the roles of animal companions and animal-assisted interventions

This review discusses existing and developing state-of-the-art noninvasive methods for quantifying the effects of integrative medicine (IM) in aging populations. The medical conditions of elderly patients are often more complex than those of younger adults, making the multifaceted approach of IM particularly suitable for aging populations. However, because IM interventions are multidimensional, it has been difficult to examine their effectiveness and mechanisms of action. Optimal assessment of IM intervention effects in the elderly should include a multifaceted approach, utilizing advanced analytic methods to integrate psychological, behavioral, physiological, and biomolecular measures of a patient's response to IM treatment. Research is presented describing methods for collecting and analyzing psychological data; wearable unobtrusive devices for monitoring heart rate variability, activity and other behavioral responses in real time; immunochemical methods for noninvasive molecular biomarker analysis, and considerations and analytical approaches for the integration of these measures. The combination of methods and devices presented in this review will provide new approaches for evaluating the effects of IM interventions in real-life ambulatory settings of older adults, and will extend the concept of mobile health to the domains of IM and healthy aging.

Perry Skeath

Papers

A wearable patch for continuous monitoring of sweat electrolytes during exertion

Quantification of cortisol in human eccrine sweat by liquid chromatography - tandem mass spectrometry.

Spirituality in the context of life-threatening illness and life-transforming change.

Increasing the effectiveness of palliative care through integrative modalities: conceptualizing the roles of animal companions and animal-assisted interventions

New and Future Directions in Integrative Medicine Research Methods with a Focus on Aging Populations: A Review