Perspectives on substance use among youth with chronic medical conditions and implications for clinical guidance and prevention: A qualitative study

Increasing numbers of youth globally live with a chronic illness. These youth use alcohol and marijuana at levels equal to or greater than their healthy peers and, when using, are at elevated risk for regular or problem use and adverse consequences to their condition. Little is known about whether behavioral theories commonly invoked to explain adolescent substance use apply to this group, limiting our ability to develop, tailor and target preventive interventions. We interviewed youth ages 16–19 years in care for a chronic disease to gain knowledge of this group’s perspectives on substance use risk, decision-making, and preferences for clinical guidance. Interviews were transcribed and thematically analyzed. Three principal themes emerged: first, having a chronic disease frames understanding of and commitment to health protecting behaviors and impacts decisions to avoid behaviors that carry risks for disease complications and flares; second, developmental impulses typical of adolescence can amplify an adolescent’s propensity to take risks despite medical vulnerability and direct youth toward maladaptive choices to mitigate risk; and third, poor knowledge about effects of substance use on specific features of a disease shapes perceived risk and undermines health protecting decisions. Youth navigate these issues variously including by avoiding substance use at a specific time or entirely, using while cognitively discounting risks and/or adjusting treatment outside of medical advice. Their perceptions about substance use are complex and reveal tension among choices reflecting a chronic illness frame, developmental impulses, and knowledge gaps. Delivery of targeted guidance in healthcare settings may help youth navigate this complexity and connect patient-centered goals to optimize health with health protecting behavioral decisions.

Introduction Today's population includes an unprecedented number of adolescents-some 1.8 billion globally [1]; 22.9% of the US population is less than 18 years of age [2]. While adolescents are generally considered a healthy group, in the US one-of-four is growing up with a chronic disease as are sizeable percentages of youth elsewhere [3]. Youth affected by chronic illness experience significant levels of disease and treatment burden (e.g., pain and medication side effects), which undermine wellbeing, lead to frequent and costly healthcare utilization [4] and family financial problems [4]. By adulthood, chronically ill youth face outsize risks for poor educational, relationship, economic and health outcomes [5,6]. Lifecourse risks reflect the complex interplay of disease and treatment experiences and the cumulative effects of social isolation, victimization, school disruption, psychological injury and home life strain [7]. Substance use poses a unique and modifiable health risk for these youth that may worsen a myriad of life outcomes, underscoring the importance of its prevention.
Alcohol and marijuana use often begins and escalates, in adolescence [8,9]. These behaviors are influenced by many factors including a natural drive towards rewarding activities [10], the availability of substances [11], modeling of peer behaviors [12,13], and perceptions of harm and benefit [14][15][16]. Health behavior theories centered on cognitive and social processes encapsulate these factors [17] and have been used to inform substance use preventive interventions [13]. For the many US youth with a chronic medical condition (YCMC) [3], and the growing percentage of youth globally with a chronic disease [18][19][20][21][22][23][24][25], decisions regarding substance use may be further influenced by their knowledge and concerns about the effects of substances on their health overall, their condition specifically and its treatment.
Research with US samples indicates that substance use is prevalent among YCMC: approximately one-third drink alcohol in high school of which one-third do so at a binge level; onefifth use marijuana [26]. Compared to their healthy peers, YCMC are as likely to initiate alcohol use and more likely to initiate tobacco and marijuana use in early adolescence (ages 14 or younger); once using these substances, they are more likely to progress to regular or heavy/ problem use by late adolescence/young adulthood [26,27]. For all youth, substance use poses risks for acute harm from accident and injury [28]. For YCMC, substance use poses additional risks from adverse medication interactions [29], increased treatment non-adherence [26], and poor disease control [30]. Indeed awareness of these factors contributes to reduced alcohol use among youth taking medications that have alcohol use contraindications. [31] To date however, few studies have considered how insights from behavioral theories stipulating important sources of influence on substance use might apply to medically vulnerable youth specifically. Gaps limit our ability to develop, tailor, and target to YCMC substance use-related preventive interventions and clinical guidance.
Prevention efforts grounded in communicating information about health risks related to substance use are common [32][33][34][35]. They emphasize perceived susceptibility to a health threat, seriousness or severity of the threat, and appraisal that steps to reduce the threat are achievable and beneficial (consistent with dimensions of Health Belief and Social Cognitive Models) [32,35,36]. Generally speaking, interventions that center solely on these factors have limited utility for preventing adolescent substance use [37]-perhaps due in part to neurodevelopmental patterns affecting judgment and decision-making. Brain maturation in early adolescence occurs in regions of the brain that are tuned to exploration, sensation seeking and sociability; maturation in early adulthood occurs in regions that govern deliberative reflection and are best suited to considering risks [10,38,39]. This normal developmental progression may leave adolescents susceptible to the appeal of exciting and social stimuli at a time during which they are less able to reflect on and revise behaviors to avoid harm. Despite this, it is possible that information about specific health risks might be valued by and impactful for youth with a chronic disease. These youth have firsthand experience with serious health harms and may experience a heightened sense of susceptibility with strong motivation to avoid risks, potentially boosting the value of well targeted guidance. While behavioral theories that emphasize social norms and peer influence on substance use behaviors [40,41] might also be relevant, they too may imperfectly apply to medically vulnerable youth who may not fully identify with the norms, models and activities of healthy peers. Similarly theories that emphasize the role of supply-side factors including advertising and promotion of substances [42] may poorly explain YCMC substance use if priorities to remain symptom free, in control, clear-headed and attuned to a disease state override the appeal of market-based patterns. These issues are not straightforward since youth with a chronic illness may perceive that substance use confers condition-related benefits and a means to escape having a disease, relieve anxiety, and in the case of marijuana address symptoms or treatment side effects.
In light of these complexities and the clear need to identify leverage points to delay and reduce substance use among youth with chronic illness, we undertook a qualitative study of beliefs and attitudes toward substance use among adolescents growing up with a chronic illness. We sought to understand factors that contribute to YCMC decision-making around substance use and to elicit preferences for the content and delivery of clinical guidance that could contribute toward risk-reducing and health promoting decisions by tapping into concerns related to patient-centered harms and outcomes.

Participant selection
Participants were recruited from an existing cohort of youth enrolled in a clinic-based validation study of a brief screening tool for assessing alcohol use risk among YCMC [26]. Details of the parent study are described elsewhere [26]. All youth had been diagnosed for at least one year. For this qualitative study, purposive sampling was used to select and interview a subgroup of eligible adolescents ages 16 to 19 years that represented a mix of gender, disease type, and history of substance use. Participants who opted out of research re-contact in the parent study or were unable to participate in a private narrative interview were ineligible. Participants were mailed a $25 gift card as compensation for their participation. The Boston Children's Hospital Institutional Review Board approved the study with a waiver of parental consent for youth participants under the age of 18 years. All participants provided age-appropriate verbal consent/assent.

Interviews
Telephone interviews were conducted in English by one or two researchers (PKS and LR) calling from a private office and lasted between 30 and 90 minutes. Interviewers were both female, had been trained in qualitative research interviewing using non-directive language, had one to two years of prior research experience recruiting similarly aged adolescents for clinical epidemiologic studies. Interviews were conducted by telephone for convenience and to reduce barriers to participation for adolescents, who can be a hard to reach group, and given the potential that eligible participants might live at some distance from the hospital and research site. The research team did not have clinical relationships with study subjects. Interviews were conducted at a time requested by participants, to optimize convenience and privacy and to limit burden. To participate in the interviews, participants were asked whether they were in a private place where they would not be overheard-all participants verbally affirmed this. Interviews were audio-recorded with participant permission and transcribed verbatim.
Interviews followed a semi-structured guide (see Supplemental Information) developed to explore daily experiences of the patient's medical condition, and to elicit information about personal, social, situational, and clinical factors affecting decision-making around alcohol and marijuana use. Preferences for clinical communication about substance use were also elicited. Questions were grounded in social cognitive theories of adolescent risk taking and focused on perceived risk of substance use [15,[43][44][45] and the salience of social influences on health behaviors [16,[46][47][48]. Interviews were undertaken in three waves over the course of one year to enable the study team to refine the question guide in response to emerging findings, and to afford opportunity to expand upon and validate themes consistent with pragmatic goals of balancing codes developed using deductive (theory-based or a priori) and inductive (emergent) approaches [49] [50][51] [52].

Data analysis
All interviews were transcribed and texts were then analyzed using an iterative, process that included within and across transcript coding to identify emergent themes, consistent with prior work [53,54] following a grounded theory approach [55,56]. Two analysts (PKS and LR) collaboratively generated an initial coding framework, informed by theory [57]. This framework evolved during transcript review from annotation of major themes using open coding (i.e., the chronic illness experience) to articulation of subthemes and constructs using axial and selective coding. Each analyst independently read and coded each transcript, labeling and organizing themes into notes for joint review and discussion. As refinement of the coding scheme progressed, principal and subordinate themes were specified that reflected areas of consistent commonality across the sample, i.e., ideas that were reflected in responses from the large majority or all participants. Data were organized into major and minor or subordinate themes and data tables were developed populated with quotes representing comments from all of the study participants. The process was iterative, and reflected both deductive and inductive processes: development of initial interview questions drew on principles of existing social behavioral theories (a deductive process) while content coding of themes/observations and stories shared by participants was undertaken to arrive at areas of meaning for this sample (an inductive process). Multiple rounds of selective coding were undertaken by the team to group themes and subthemes into a coherent model. Finally the set of exemplary quotes used in the data tables was winnowed and reduced for final reporting. Study principal investigators (ERW and SL) reviewed the coding scheme, themes and tables for coherence, consistency, and correspondence with transcripts. Interviewing continued until thematic saturation was reached (achieved for 31 youth) under a consensus-driven process. Methods and reporting align with comprehensive standards for qualitative research [58].

Sample characteristics
In total, 36 youth consented to participate of 39 who were invited (92.3% consent rate). Thirtyone youth completed an interview (participation rate 79.5%, non-completion was due to youth scheduling difficulties). Six interviews conducted with patients with attention-deficit/hyperactivity disorder (ADHD) were excluded from the final sample due to the fundamental differences between neurodevelopmental conditions (i.e., ADHD) and the physical conditions affecting the majority of the sample. The final sample comprised 25 youth (14 female) aged 16-19 years (mean age = 18.0): 11 with a rheumatic disease, including two with inflammatory bowel disease (IBD)-associated arthritis and eight with juvenile idiopathic arthritis (JIA), and one with polymyositis; four with IBD only; nine with Type 1 diabetes (T1D); and one with moderate persistent asthma. The sample was predominantly white, and most participants reported at least one parent with a college education living with them at home (see Table 1). The average age of diagnosis was eight years, and on average, participants visited the subspecialty care clinic where they were originally enrolled 3.4 times in the year preceding enrollment into the parent study.

Principal themes
Three principal themes emerged around substance use decision-making. The first theme, the chronic disease frame, describes ways in which living with and managing a chronic condition shapes how affected youth view and approach the world and within that, understand and commit to health behaviors. The second theme, the adolescent frame, pertains to the influence on substance use decision-making of developmental status, attendant impulses toward novelty and experimentation, and sensitivity to social influences. The third theme, disease-specific substance use knowledge, encompasses understanding of the connections between substance use and a chronic condition as they may influence perceived risk and vulnerability, and within that preferences for content and delivery of substance-use related education and guidance.

Theme 1: The chronic disease frame
For participating youth, living with and managing their chronic condition shapes the way they define self and experience life. This chronic disease frame pervades decision-making about health behaviors. Youth reported a strong sense of health consciousness centered on avoiding  disease complications. Substance use decisions were filtered through this lens. Consideration of health and well-being motivated youth to abstain from or moderate substance use or, in some cases, prompted use for instrumental purposes, such as to relieve pain or symptoms (Table 2). Subthemes are outlined below. Impact of condition on daily life and identity. Having a chronic condition was inextricably tied with everyday life, and for some youth constituted a stable feature of self and identity. Having a chronic condition increased some youth's sense of inner strength (hardiness), conferring empathy and perspective; others had not fully reconciled their condition as a permanent feature of life and self. Youth described this coming to terms with their condition as a process that included accepting responsibility for disease management and becoming motivated to preserve health. Many participants reported feeling a sense of accelerated maturity and greater life experience relative to their peers which stemmed from having to manage their  condition. Where present, this diminished their interest in heavy and in some cases any substance use. Others felt that time spent away from their peers for health reasons interrupted their social maturation; in rare cases, youth viewed substance use a means of catching up and behaving in an age or developmental stage appropriate fashion. Daily disease experience and adjustment to having a chronic condition were integrally connected to health-related decision-making. Youth reported high value for minimizing illness intrusiveness and disease-related hassles-whether short-term interruptions (e.g., missing class for "15 minutes here, 15 minutes there" to check blood sugar, as shared by a participant with Type 1 diabetes), or larger dislocations (e.g., "having to drop out of school and get my GED (general education diploma) [due to arthritis flares]," an example given by a participant with JIA). Being healthy was highly motivating and conceptualized as living complication-free and unimpeded in activities.
Health-conscious influences on substance use decisions. Consciousness about health status and vulnerability played a central role in participants' decisions around substance use. When discussing their decision-making process, youth reflected on how drinking may complicate their condition. Many cited concerns about the interaction of alcohol with their medications. Others worried about short-term consequences, such as acute hypoglycemia for youth with type 1 diabetes. The presence or absence of physical symptoms weighed into this group's immediate decision-making, and many youth reported deferring substance use/abstaining when symptomatic. Participants were acutely aware of the need to stay physiologically and cognitively attuned to their symptoms, and worried that being under the influence could cloud perception of somatic information necessary to staying aware of their disease state. The perception that using substances may ameliorate symptoms also factored into participants' decisions to use substances. Some youth reported using marijuana for pain relief or for "stomach calming" effects in the case of IBD.

Theme 2: The adolescent stage
When discussing their substance use decisions, youth cited motivations and influences typical of their developmental status-these included valuing novelty and autonomy, being sensitive to the impact of social (peer) influences, attunement to descriptive and injunctive norms, and the availability of appealing alternatives. For some youth, the desire to protect one's health conflicted with adolescent-typical impulses to experiment, fueling resistance to using substances. For others, experience of social influences and/or impulses toward novelty and experimentation tipped decision-making toward risk behaviors. Where influences moved youth toward risk, participants reported employing a range of behavioral and cognitive strategies to reconcile the dissonance they felt between the threat to health from substance use and their concern to be healthy, and avoid complications and flares (Table 3). Subthemes are outlined below.
Developmental impulses. The appeal of novel experiences and an impulse for experimentation were drivers of substance use, especially initiation. Reactance against rules was, for some, a reinforcing factor. Across the sample, youth placed high value on autonomy which was central to personal decisions to abstain from as well as use substances. Youth evaluated their own and peer behaviors similarly; several described peer behaviors as reflecting "personal choice." Preserving autonomy and self-determination and assuming a non-judgmental stance even for unhealthy behaviors are core values for this age group.
Social and contextual influences. Youth reported sensitivity to peer behaviors and norms. Associating with friends who use substances provided an opportunity to observe harms resulting from use and also to consider benefits; both positive and negative consequences of using were evident in stories youth shared about friends' substance use. Participants also reported obtaining substances from friends, a factor contributing to use. A perceived lack of attractive social alternatives increased desire to use substances to relieve boredom or conform socially. Engagement and commitment to prosocial activities (e.g., academics) as well as availability of appealing sober social opportunities (e.g., watching movies with friends) supported decisions not to use. Balancing adolescent impulses and chronic disease concerns. Participants employed a range of cognitive and behavioral strategies to reconcile the dissonance they experienced between the developmentally driven appeal of substance use-i.e., value placed on novelty, experimentation, sociability, and conformity-and the potential that substance use would jeopardize their health and/or contribute to disease exacerbations or flares. An area of acute dissonance reflected concern for potential risks stemming from simultaneous exposure to alcohol and alcohol-interactive medications. Youth took several behavioral steps to counter this risk. Some youth adjusted treatment regimens without clinical guidance, skipped medications, or spaced out the timing between taking a medication and using alcohol to avoid potentially harmful interactions. Those with T1D mentioned increasing the frequency of blood glucose monitoring and strategically adjusting their insulin and food intake to compensate for alcohol use. Substitution served as an additional behavioral strategy. Several participants opted for avoiding alcohol and using marijuana on select occasions; these youth perceived marijuana to be less health-compromising and non-interactive with medications. Cognitive strategies were evident too. To cope with concerns about their health, participants minimized perceived risks associated with substance use. Some rationalized that their level of alcohol use does not rise to the level of clinically significant abuse or a disorder-a cognitive strategy that, even if true, ignores any special risk from substance use for this group given their medical condition.

Theme 3: Disease-specific substance use knowledge
Participants were curious about how substance use affects their condition and its treatment, indicating gaps in understanding. They were eager to discuss these issues during their specialty care visits and expressed clear preferences for content of messages and their delivery (Table 4). Subthemes are outlined below.
Information deficits. Many participants indicated that substance use harms are not clearly or consistently discussed as part of subspecialty medical care. Consequently, participants had unanswered questions about the impact of substance use on their condition and its treatment.
To lessen these gaps in understanding, many youth independently sought information, including through online sources. Some were unconvinced by what they considered to be a cursory discussion of harms held with their physician and sought confirmatory or supplemental information from alternative sources. Inattention to these issues within healthcare settings created room for inaccurate or misguided information from peers or others to shape participant beliefs and behaviors. made an impression on me is probably the fact that the glucagon wouldn't work if I was severely intoxicated. . .I think that's the thing that I'd really say scared me the most because that's kind of a scary thought that like, you could die from drinking because your blood sugar was low and they had no way-and even in the hospital, they can give you IV's and stuff, but they really can't do much for you until the alcohol has been processed through your system. ( Perspectives on substance use among youth with chronic medical conditions Preferences for content and delivery of substance use messages. Youth voiced strong preferences for bridging the topics of substance use and their chronic condition in a manner that is factual and specific. Participants asserted that this information would be best delivered by their specialist who they considered the expert on their body and condition.
A common theme was a preference for a direct and honest discussion about the diseasespecific risks of substance use without "any gray area" or "sugar-coating." When clinicians did not directly articulate the risks or recommend cessation, participants sometimes interpreted this as tacit granting of permission to use substances. Youth appreciated when providers demonstrated sensitivity to their developmental context and the social pressures they face. Further, communicating real-life examples of substance use harms served to humanize messages about substance use. Finally, many youth expressed that time alone with their provider and assurances of confidentiality were necessary to creating a safe space for honest discussion and disclosure.

Discussion
In this investigation, we found that among youth with a chronic illness, decision-making about substance use is integrally related to their experiences living with and managing their chronic condition. Awareness of having a chronic illness provides an omnipresent frame of reference which bears on the many calculations youth make about how to manage their condition and assess safety and risk. This frame and the life experiences of this group may prepare them to perceive substance use-related health risks as serious or severe-a vital toehold for prevention. The developmental stage of adolescence and the appeal of novelty and experimentation play a role in risk perception and behavioral decision-making, as may the perceived benefits of using substances (particularly marijuana) to address symptoms and treatment side effects. However findings suggest that these factors may not outweigh the influence of messages that speak directly to how substance use can amplify medical vulnerabilities. Rather, clear guidance and messaging about these issues are welcomed and valued by youth. While prevention efforts will need to consider the push-pull among these factors, findings suggest that youth are primed to prioritize behaviors aligned with maintaining disease control and symptom quiescence over those that reinforce novelty and sociability. Indeed, the deeply personal lived experience of a chronic illness and attendant disease and treatment burdens create the potential to harness affective, experiential and deliberative components of risk perception [59] for impactful interventions. Findings overall bear on development of clinical services to prevent and reduce substance use among medically vulnerable youth, and provide insight into how dimensions of behavioral theories might be adapted to guide such efforts by emphasizing messaging that speaks to the unique concerns and experiences of these youth.
Several issues may be particularly salient when intervening with this group. These include delivery of factual and disease-specific messages about substance use risks and guidance around the importance of avoiding substance use. Youth favored this type of guidance and its absence may leave cognitive "wiggle room" sufficient to enabling unhealthy choices. Overall, narratives revealed tendencies toward denial, minimization of risk, and an inflated sense of control over risk management. Lack of specific information also provides a context in which youth may perceive near term benefits of use to relieve symptoms, in the case of marijuana, without access to specific information concerning risks to health long-term.
YCMC perceived a disconnect between substance use behaviors and their value for healthrelief from cognitive dissonance was sought at times by efforts to alter treatment regimens to accommodate drinking (i.e., changing dosing, scheduling, and adherence to medications), as opposed to choosing abstinence. Helping youth understand and internalize substance use risks and prioritize concerns to protect their health over social and developmental influences may foster consistent healthy decision-making and better outcomes. Prior research has shown that poor knowledge about the potential for alcohol interactions with medications and laboratory tests is associated with sharply elevated risks of alcohol use and binge drinking among YCMC as well as regular medication non-adherence [26,31] Addressing these issues as part of a targeted preventive intervention may offer valuable guidance that contributes to health protecting choices and actions.
Learning how to effectively harness medically vulnerable adolescents' cognitions, motivations, and health concerns to support positive decision making may be especially important. Findings from developmental neuroscience suggest the difficulty of countermanding the socially and physiologically reinforcing effects of substance use behaviors on reward pathways instantiated in the adolescent brain [60][61][62][63] which mature prior to those that center on consequential thinking [10,60]. In this context, it is vitally important to develop preventive messages that are patient-centered and persuasively impact top concerns and motivations of medically vulnerable youth; identifying key touch points may offer the traction necessary for messages to align with established values and priorities to prevent disease exacerbations by avoiding substance use and motivating healthy choices.
YCMC prefer information that connects substance use risks to impacts on their condition and favor messaging delivered by health experts with whom they have a trusting relationship. Locating psycho-educational prevention in pediatric specialty care was highly acceptable and preferred by these youth who also reported they value being asked direct questions about health risk behaviors in confidence, consistent with reports of healthy teens [64][65][66] and teens with chronic medical conditions [67]. Thus, provision of confidential verbal screening with unambiguous questions followed by clear advice about avoiding or resisting substance use while acknowledging the potential for conflicting social developmental pressures may be key features of a successful clinical conversation that aligns with national priorities for adolescentfriendly clinical preventive services [68]. Participants reported that discussions about substance use are not occurring during subspecialty visits or feel perfunctory and unsatisfying. This finding mirrors the low rates of alcohol screening and counseling among pediatric subspecialists found in the most recently published survey reports [69,70].
Qualitative interviews undertaken for this study afford insight into motivations and decision-making around substance use and elucidate aspects of substance use screening and messaging that are valued by medically vulnerable youth. Findings may inform preventive interventions and build on epidemiologic reports about YCMC risks [26,27,71]. In this context several limitations of this research merit mention. The sample represents a mix of conditions and patient background characteristics, however interviews were conducted with patients at a single institution and findings may not generalize. The sample is predominantly white and most participants reported parents with some college education which, while consistent with clinic demographics, could exclude youth from minority and other vulnerable backgrounds. Youth understanding and interpretation of past events are especially relevant to constructing salient health messages and capturing youth perspectives was the focus of this investigation. Nevertheless, recall and social desirability biases can affect the accuracy of participant reports, especially in qualitative work. For these reasons interviewers prefaced each interview with the open-ended aim of the study, offered assurances of confidentiality, and took a curious, nonjudgmental stance.

Conclusions
Findings point to the need for clinicians-especially pediatric specialists-to provide substance use education and guidance to YCMC that connects risks and recommendations to patient-centered disease-specific concerns and goals. Nuanced interventions are needed that address the complexity of navigating chronic disease management and adolescent-typical impulses and pressures. Development and evaluation of tailored, targeted prevention messages and programs that engage youth in thoughtful, respectful, and impactful discussions about their risks and choices are important next steps to protecting the health of medically vulnerable youth.
Supporting information S1 File. Interview guide. This is the semi-structured interview guide. (DOCX) S2 File. Excerpts of quotes relevant to study. This is the listing of quotes used in the study. (PDF)