What is the future of digital tools to help manage pain in sickle cell disease patients?

KEYWORDS:

• Sickle cell disease
• self-management
• mHealth
• smartphones
• smartwatches
• digital health interventions
• sensors

1. Introduction

1.1. Sickle cell disease

Sickle cell disease (SCD) refers to a group of related autosomal recessive disorders of the hemoglobin beta gene (HBB) structure. Affected individuals are either homozygous for the sickle mutation or are compound heterozygous for the sickle mutation and another abnormal HBB mutation whose protein participates in the formation of a hemoglobin polymer under deoxygenated conditions. These mutations arose in Africa, and were spread by outmigration to Southern Europe, the Middle East, and India. The African slave trade subsequently brought the mutation to areas in the US, the Caribbean, and South America, particularly Brazil. Over 100,000 individuals are impacted by this disease in the US and over 25 million worldwide, mostly in lower- and middle-income countries (LMIC) in Sub-Saharan Africa.

Polymerization of sickle hemoglobin leads to poorly deformable erythrocytes that can occlude susceptible vascular beds, leading to ischemia-reperfusion injury and a complex inflammatory process that stimulates peripheral nociceptors. These stimulated nociceptors initiate an equally complex process in the peripheral and central nervous systems ultimately experienced by the individual as acute pain. These painful episodes (often termed ‘crises’) start in early infancy as fetal hemoglobin levels fall, and are unpredictable in occurrence, severity, duration, and body location. Repeated painful episodes are thought to cause a poorly understood sensitization process of the peripheral and central nervous systems in many adolescents and young adults leading to the common experience of chronic pain, and may also enhance the perception of acute pain. Pharmacologic and non-pharmacologic strategies are recommended for management of sickle pain in hospitalized patients, as well as for those seeking to self-manage pain in the home setting [1].

1.2. Self-management

Self-management is conceptualized as a self-motivated and collaborative process, involving patients, their family members, and healthcare providers, to recognize and track symptoms, appropriately modify family, social and work/school roles, manage often complex medication regimens, develop strategies to deal with the psychological consequences of illness or symptoms, and interact with the healthcare system [2]. Mobile healthcare (mHealth) using digital technologies is an innovative approach to facilitate self-management for adolescents and young adults (AYAs) given the ubiquity of smartphones in this age group capable of accessing a large number of health-related internet applications (apps), as well as available consumer-oriented wearable devices, such as smartwatches and other devices, broadly categorized as ‘wearables’ [3]. Tablets and headsets are also available to support immersive and non-immersive virtual reality (VR) programs for pain management [4]. Smartphones and tablets are also convenient devices for recording patient-reported outcome measures that can provide valuable monitoring data for both research and clinical outcomes.

2. Digital tools

2.1. Mobile self-management apps

A number of recent reviews have described the increasing number of apps accessible using smartphones available for tracking, assessing, and managing acute pain [5], pediatric chronic pain [6], and SCD [7]. Some of these apps may also contain disease- or pain-related educational materials or assist with medication adherence. For example, iManage is an app that features daily tracking of pain, fatigue, and mood symptoms; ability to choose individual self-management goals and visually track progress; visual calendar that links SCD symptoms and self-management behaviors/goals; and a peer support function [8]. Similarly, iCanCope with Sickle Cell Disease uses a website to deliver pain education, and a mobile app to teach cognitive-behavioral therapy pain management in a digital format, to enhance self-efficacy for AYAs managing SCD pain. A randomized clinical trial demonstrated that the use of this app significantly reduced average pain intensity from baseline to 6-month follow-up, and reduced the number of days with pain [9]. Concerns about limited user engagement and health literacy impacting mobile app efficacy have prompted the inclusion of peer health coaches or the use of conversational agents (chatbots) to enhance patients’ self-management and support health behavior changes [10]. These online self-management behavioral interventions may reduce current self-management barriers, such as issues of mobility, transportation, work/school time constraints, or access to specialized providers. Apps also allow individuals to tailor interventions by selecting additional topics of interest or concern, review materials as needed, and to continue self-management support outside of a specific number of scheduled sessions.

2.2. Devices

Smartwatches have substantial capabilities as passive sensors potentially useful for monitoring the physiological impact of SCD pain symptoms [11]. All have nine-axis inertial motion sensors that track motion and position in three-dimensional space, which can be displayed as measures of physical activity such as step counts, distance traveled, exercise minutes, etc. Green-light-emitting diodes in these devices detect an optical signal using reflectance photoplethysmography that measures local tissue arterial blood volume, which can be used to monitor a variety of physiologic parameters, such as heart and respiratory rates. Some recent smartwatches, as well as research-grade wearable devices, use reflectance pulse oximetry to estimate oxygen saturation. A few research-grade devices are also capable of collecting additional data that may provide insights into the pain experience, such as skin conductance response as measured by superficial electrodermal activity [12].

Such sensors could have a number of potential uses in the management of sickle pain. Measures of physical activity can detect changes in activity and sleep duration/interruptions frequently caused by acute and chronic pain. Physiologic measures, such as heart/respiratory rate or oxygen saturation, can be altered by acute pain. Heart rate variability can be calculated from these data as an index of the autonomic nervous system activity related to reactivity to pain stimuli. Such data from Apple and Microsoft smartwatches have shown correlations with changes in self-reported pain intensity scores resulting from analgesic management of pain episodes during in-patient or day hospital admissions [13,14]. Results from these algorithms could provide objective physiologic data to supplement subjective pain intensity and other patient-reported outcomes during clinical trials of novel analgesics to diminish pain, or of drugs to more quickly resolve painful episodes in hospitalized patients, or to monitor patients during similar decentralized clinical trials in the home setting. Such monitoring might also facilitate early hospital discharges with subsequent supervised home pain management, or reduce the frequency of subsequent early re-admissions for pain treatment. Data from research grade wearables have also been used to predict the onset of a painful episodes, which might facilitate early treatment and avoid hospitalizations [15].

3. Expert opinion

In this editorial, I have discussed the future of digital tools to help manage pain in patients living with SCD. Digital tools in the mHealth space have considerable potential to improve the management of pain in persons living with SCD by facilitating data collection and providing access to interventions that promote self-management skills. Patient-generated data could be combined with other healthcare data to inform clinical judgments. Such data could facilitate a precision medicine approach to the unique treatment needs of each patient, but will require progress in data standards and infrastructure, while ensuring privacy and security. For example, a data-driven approach could identify individuals progressing from intermittent acute pain to chronic pain and guide early targeted interventions. Advancements in design of wearable sensors and visual displays, and further use of machine learning/artificial intelligence, will promote new opportunities for use of these digital tools to help manage pain.

Use of digital technologies to deliver behavioral interventions has the potential to reach an increasing large number of individuals living with SCD who would not usually have access to these treatments, but many digital interventions have not been broadly tested or implemented outside of a research setting. While many provide peer social support, linkages to primary healthcare providers or other healthcare professionals for long-term support are often poor. Readability of content and poor usability may discourage use of apps by individuals of limited health literacy, while cost concerns may limit use of smartphones, smartwatches, or VR headsets. Limited participant engagement in these apps has been identified in a number of studies, and will likely require further design and content improvements to better adapt to the needs of minority populations, younger children, or persons living in LMIC countries.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.