Need for Behavioral Interventions for Young Adults Living with Advanced Cancer in the U.S.

The population of young adults (YAs) aged 18-39 living with advanced cancer is growing and faces a compounded set of challenges at the intersection of age and disease. Despite these substantial challenges, behavioral interventions tailored to YAs living with advanced cancer remain scarce. This commentary aims to (1) discuss the unmet psychological, social, and behavioral needs of YAs living with advanced cancer; (2) highlight the paucity of behavioral interventions tailored to this growing population; (3) offer recommendations for the development of behavioral interventions targeting the unique needs of YAs living with advanced cancer; and (4) describe potential far-reaching public health benefits of these targeted behavioral interventions.

Social isolation and social connectedness among young adult cancer survivors: A systematic review.

BACKGROUND: Social isolation and connectedness are social determinants of health that have demonstrated effects on cancer-related outcomes. These constructs have been systematically evaluated among pediatric and older adult cancer populations. In this review, the authors evaluated the prevalence, correlates, and psychosocial implications of social isolation and connectedness among young adult (YA) cancer survivors aged 18-39 years. METHODS: Peer-reviewed articles published in English before June 2021 were identified from database searches and included articles' reference lists according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included articles described studies that assessed social isolation and/or connectedness among YA cancer survivors. RESULTS: In total, 5094 unique records were identified; 4143 were excluded after title/abstract screening, and 907 were excluded after full-text review. Forty-four articles were included. Few studies used validated measures or directly assessed social isolation or connectedness. Social isolation was similarly prevalent among YAs and older cancer survivors and noncancer populations. Demographic, clinical, and behavioral risk and protective factors for social isolation were identified. Social isolation was related to worse psychological well-being, whereas social connectedness was often, but not always, related to better psychological well-being. CONCLUSIONS: This growing literature underscores the relevance of social isolation and connectedness as important health determinants among YA cancer survivors. The identified risk and protective factors can identify YAs who especially may benefit from screening for social isolation. Future studies are needed that directly, reliably, and validly evaluate social isolation and connectedness to inform the development of interventions to decrease isolation and increase connectedness.

Development and initial testing of TOGETHER-YA: an eHealth-delivered and group-based psychosocial intervention for young adult cancer survivors.

PURPOSE: This study aimed to (1) develop TOGETHER-YA, an e-Health-delivered and group-based health-related quality of life (HRQOL) intervention for young adult (YA) cancer survivors aged 18-39 (Part 1), and (2) determine its initial feasibility and acceptability in a single-arm pilot trial (Part 2). METHODS: TOGETHER-YA is a manualized, 10-week intervention for YA survivors that includes elements of relaxation training, cognitive-behavioral therapy, and health education. In Part 1, content was adapted from existing evidence-based interventions with feedback from YAs (N = 22) in four iterative focus groups. In Part 2, YA survivors (N = 11) participated in a single-arm pilot trial of TOGETHER-YA. Intervention groups were led by a trained facilitator over videoconference. Primary outcomes were feasibility (i.e., recruitment, session attendance, retention) and acceptability (i.e., participant satisfaction). RESULTS: Focus groups reacted positively to TOGETHER-YA and provided actionable recommendations for enhancing its relevance and acceptability, which were implemented. In initial testing, all feasibility and acceptability benchmarks were met; 58% of eligible YAs were recruited, participants attended M = 6 intervention sessions (SD = 3), and 82% of participants were retained post-intervention. On average, participants "agreed" to "strongly agreed" with positive statements about the weekly sessions and the overall program. CONCLUSION: TOGETHER-YA was developed in collaboration with YA cancer survivors and found to be feasible and acceptable in initial testing. TOGETHER-YA is the first HRQOL intervention for a broad range of YA survivors that is eHealth-delivered for convenience and group-based for peer support. Future large-scale trials should test its efficacy for improving HRQOL. TRIAL REGISTRATION: NCT05048316, September 17, 2021; NCT05054569, September 23, 2021.

Preliminary Effects of Mindfulness Training on Inflammatory Markers and Blood Pressure in Young Adult Survivors of Cancer: Secondary Analysis of a Pilot Randomized Controlled Trial.

BACKGROUND: This was a secondary analysis of a pilot randomized controlled trial (RCT) of mindfulness-based stress reduction (MBSR) among young adult (YA) survivors of cancer, which showed preliminary evidence for improving psychosocial outcomes. Secondary outcomes assessed were the feasibility of collecting biological data from YAs and preliminary effects of MBSR on markers of inflammation and cardiovascular function. METHOD: Participants were randomized to 8-week MBSR or a waitlist control condition. Participants provided whole blood spot samples for analysis of C-reactive protein (CRP) and interleukin (IL)-6 as well as blood pressure data in-person at baseline and 16-week follow-up. Feasibility was assessed with rates of providing biological data. Linear mixed effects modeling was used to evaluate preliminary effects of MBSR on inflammatory markers and blood pressure over time. RESULTS: Of 126 total participants enrolled, 77% provided biological data at baseline (n = 48/67 MBSR, n = 49/59 control). At 16 weeks, 97% of the 76 retained participants provided follow-up biological data (n = 34/35 MBSR, n = 40/41 control). Relative to the control group, MBSR was associated with decreased systolic blood pressure (p = 0.042, effect sizes (ES) = 0.45) and decreased diastolic blood pressure (p = 0.017, ES = 0.64). There were no changes in CRP or IL-6. CONCLUSION: This was the first study to explore the feasibility of collecting biological data from YA survivors of cancer and assess preliminary effects of MBSR on inflammatory and cardiovascular markers in an RCT. Minimally invasive biological data collection methods were feasible. Results provide preliminary evidence for the role of MBSR in improving cardiovascular outcomes in this population, and results should be replicated.

A qualitative assessment of body image in adolescents and young adults (AYAs) with cancer.

CONTEXT: Among adolescents and young adults (AYAs), cancer and its treatment can disturb body image in distinct ways compared to younger or older individuals. OBJECTIVE: Since AYA body image is not well understood, this study was designed to develop a conceptual framework for body image in AYAs with cancer. METHODS: Concept elicitation interviews were conducted with 36 AYA patients [10 adolescents (15-17 years), 12 emerging adults (18-25 years), 14 young adults (26-39 years)] and health care providers (n = 36). The constant comparative method was used to analyze for themes and properties, with themes considered saturated if they were present and salient across participant sets. RESULTS: Twenty themes emerged from participant data. Three themes illustrate a shared understanding of patients' experience of body image: (1) physical changes produce shifts in identity and experience of self; (2) precancer body image shapes how the AYA experiences cancer-related physical changes, and (3) changes to the body are upsetting. Nine themes were unique to patients while eight themes were unique to providers. Patient body image experiences were found to evolve over time, largely affected by concerns about how others view them. Providers appeared attuned to AYA patient body image but recognized that it is not systematically addressed with patients. CONCLUSION: More striking than differences between patient groups is the consistency of themes that emerged. The conceptual framework of body image developed from these data offers an important step toward addressing body image concerns for AYA patients.

Understanding and Enhancing Support Group Participation Among Adolescent and Young Adult Cancer Survivors: The Impact of Integrating Adolescent and Young Adult Cancer Navigation Services.

This quality improvement initiative aimed to (1) explore the impact of adolescent and young adult (AYA)-specific navigation on attendance at a monthly peer support group for survivors aged 18-39 at a large comprehensive cancer center, and (2) better understanding attendees' preferences for group structure. Group attendance significantly increased following integration of AYA navigation. Using an online survey, we identified priority topics for discussion and desired changes to group organization, leading to modifications to group structure. Results highlight the value of having dedicated staff who proactively orient patients to resources tailored to their unique needs, and the importance of flexible program development that incorporates stakeholder input.

A randomized pilot study of mindfulness-based stress reduction in a young adult cancer sample: Feasibility, acceptability, and changes in patient reported outcomes.

BACKGROUND: The primary purpose of this study was to examine the feasibility and acceptability of participation in a randomized waitlist-controlled intervention of mindfulness-based stress reduction (MBSR) in a young adult cancer sample. A secondary aim was to examine patterns of change in patient reported outcomes (PROs) of physical, social, and emotional functioning. METHODS: Participants were enrolled at a large Midwestern comprehensive cancer center and randomized to MBSR or a waitlist control. Feasibility and acceptability were examined through enrollment metrics and a survey. PROs were gathered at baseline, 8-weeks, and 16-weeks. Descriptive statistics and mixed models were used in analyses. RESULTS: Of 597 eligible participants, 151 (26.5%) consented from which 126 (83.4%) completed baseline measures. Sixty-seven participants were randomized to MBSR, and 59 to the waitlist. Immediately following MBSR, the majority of respondents (72%-78%) reported their experience with mindfulness was very logical and useful to increasing their wellbeing. Compared to waitlist members, MBSR participant's scores on PROs improved in expected directions. CONCLUSIONS: Our findings suggest that recruitment for an intensive, in-person, multi-week supportive intervention can be challenging with young adults with cancer, similar to other cancer survivor populations; however once enrolled, feasibility and acceptability of MBSR was supported. Further, initial evidence on the role of MBSR on short-term changes in select PROs with this population was also demonstrated.

A Qualitative Focus Group Study to Illuminate the Lived Emotional and Social Impacts of Cancer and Its Treatment on Young Adults.

Purpose: Among the many challenges that exist among young adults with cancer, those that intersect psychosocial domains have only begun to be addressed by medical, research, and advocacy communities. While some have attempted to empirically document the psychosocial burden of adolescents and young adults (AYAs), there is a paucity of research exploring this phenomenon from the perspective of AYAs themselves. The purpose of this study is to better understand the lived experiences of young adult cancer survivors and the psychosocial impacts that cancer has had on their lives. Methods: We used qualitative focus group methodologies to elicit positive and negative psychosocial impacts of the cancer experience in a young adult cancer sample. Results: We conducted three separate focus groups (n = 16). The average age of participants was 33 and majority were female (75%), Caucasian (50%), and married (44%). The most common cancer diagnoses were breast (38%), colon (13%), and acute myeloid leukemia (13%). Participants reported experiencing multiple emotional and social impacts such as stress, sadness, and fear; identity changes; utilizing different coping strategies; challenges discussing cancer; feeling pressure to be better; feeling abandoned, misunderstood, or invisible; and experiencing role reversals with family members. Conclusions: Participants reported experiencing several emotional and social impacts of cancer on their lives, both negative and positive. Our findings are important for oncology clinical practice and survivorship research activities with young adults, especially given the presence of these impacts over the long term.

Palliative Care Usage in Young Adult Oncology Population.

Context: Early integration of palliative care (PC) into adult oncology practice has been shown to improve quality of life and health care utilization; however, little is known about PC in young adults with cancer. Objectives: Our primary objective was to determine rates and timing of PC consultation in young adult patients with advanced solid tumor cancer at a single institution. Methods: We conducted a retrospective analysis of young adults of age 18-39 years with advanced solid tumor malignancy at an urban academic medical center between June 1, 2014 and June 30, 2015. Results: Of 129 patients identified, 70 of 129 (54%) had a PC consult and 34 of 70 were inpatient-only consults. PC consults occurred for a median of 104 days before death, and for those with inpatient-only consults, PC consults occurred for a median of 18 days. Patients with worse recent Eastern Cooperative Oncology Group (ECOG) performance status were more likely to have had a PC consult (p < 0.001). Of the patients who died during the study period, patients with PC consults were more likely to have been hospitalized (72% vs. 47%), in the intensive care unit (21% vs. 0%), in the emergency room (ER) (72% vs. 47%), and have received chemotherapy (17% vs. 0%) within 30 days of death compared with those who did not have a consult; however, these differences were not statistically significant. Conclusion: In this analysis, over half of young adults with advanced solid tumors received PC consults. PC consult typically occurred for one year after diagnosis and about three months before death. Additional research is needed to identify how to better integrate PC early in this patient population and assess the resulting impact.

Future health of AYA survivors.

Adolescent and young adult (AYA) oncology patients (ages 15-39) have been identified as a group with healthcare disparities including gaps and challenges in diagnosis, access to care, research, clinical trial participation, and cure rates. Like other patient groups with cancer or other chronic illnesses, disparities can lead to poor future health and outcomes, which is a well-recognized concern within the AYA population. Cancer is the leading disease-related cause of death in this age range. Numerous interested groups including the National Cancer Institute have met to address the research and cancer care needs of AYAs. This review highlights how these gaps in care during and after treatment can affect future health of this population of patients. Access to care, models of survivorship care, and lack of provider education are discussed. Survivorship care and use of guidelines, and promotion of psychosocial support and health behaviors during treatment and beyond are essential to optimizing future health of AYA patients.

Clinical research participation among adolescent and young adults at an NCI-designated Comprehensive Cancer Center and affiliated pediatric hospital.

PURPOSE: Minimal clinical trial participation among adolescents and young adults (AYAs) with cancer limits scientific progress and ultimately their clinical care and outcomes. These analyses examine the current state of AYA clinical research participation at a Midwestern comprehensive cancer center and affiliated pediatric hospital to advise program development and increase availability of trials and AYA participation. Enrollment is examined across all diagnoses, the entire AYA age spectrum (15-39), and both cancer therapeutic and supportive care protocols. METHODS: his study was a retrospective review of electronic medical records via existing databases and registries for all AYAs. Data were collected for AYAs seen by an oncologist at the adult outpatient cancer center or at the pediatric hospital between the years 2010 and 2014. Descriptive statistics and logistic regression analyses were conducted to characterize this sample. RESULTS: In the pediatric setting, 42.3% of AYAs were enrolled in a study compared to 11.2% in the adult setting. Regression analyses in the pediatric setting revealed that AYAs with private insurance or Caucasian race were more likely to participate. Within the adult setting, ethnicity, race, insurance, and diagnosis were associated with study participation; 54.8% of study enrollments were for cancer therapeutic and 43.4% for supportive care studies. CONCLUSIONS: These results are comparable to previously published data and support the need for new local and national AYA initiatives to increase the availability of and enrollment in therapeutic clinical trials. The same is true for supportive care studies which play a crucial role in improving quality of life.

Promoting the Shared-Care Model for Adolescent and Young Adults With Cancer: Optimizing Referrals and Care Coordination With Primary Care Providers.

BACKGROUND: The "shared-care model" for patients with cancer involves care coordination between primary care providers (PCPs) and oncologists, with the goal of optimizing survivorship care. However, a high proportion of adolescent and young adult (AYA) cancer survivors do not have a PCP. Study objectives were to increase the percentage of AYAs with a PCP documented in the electronic medical record (EMR) via the use of a best practice advisory (BPA) or "stopgap" intervention; to increase communication between providers by the number of routed clinic notes; and to assess oncology providers' attitudes/beliefs about the model and intervention. METHODS: Data were collected for the 6 months before implementation of the BPA to determine the percentage of AYAs with a PCP and the number of notes routed to providers (time point 1 [T1]). The same data were collected at time point 2 (T2) after the BPA had been implemented for 6 months. Oncology providers participated in an education video module and an online survey at T1 and a survey at T2. RESULTS: At T1, 47.1% of 756 AYAs had a documented PCP in the EMR. At T2, the percentage increased to 55.1% (P<.002). The number of routed notes did not change significantly from T1 to T2. Providers that completed the intervention survey agreed/strongly agreed that the shared-care model is a desirable model of care (T1 = 86%; T2 = 93%) and that a BPA is useful for facilitating PCP referrals (T1 = 76%; T2 = 39%). CONCLUSIONS: This BPA is feasible for increasing the percentage of AYAs with a PCP documented in the EMR and could potentially lead to increased PCP referral and communication among providers for the benefit of long-term survivorship care. Providers generally agree with the shared-care model; however, the BPA implementation requires modification.

Models of Cancer Survivorship Care for Adolescents and Young Adults.

OBJECTIVES: To review the literature on adolescent and young adult (AYA) oncology, discuss survivorship models of care, and focus on the unique needs of AYA patients with transition of care from treatment to survivorship. DATA SOURCES: Peer-reviewed literature, workshop summaries, clinical practice guidelines. CONCLUSION: Advancements have been made for AYAs with regard to identifying risk factors from cancer treatment and the need for ongoing follow-up care. Survivors face several unique care transitions. Several models of survivorship care are available for AYAs. IMPLICATIONS FOR NURSING PRACTICE: The responsibilities of survivorship care for AYA patients fall on clinical providers, researchers, the government, advocacy groups as well as the survivors and families themselves. Nurses must remain cognizant and educated on AYA survivorship issues.

Physical, emotional, and social health differences between posttreatment young adults with cancer and matched healthy controls.

BACKGROUND: Young adults (YAs; ages 18-39 years) with cancer face interrupted developmental milestones and increased stressors that can adversely influence psychosocial adjustment. Transitioning from active treatment to posttreatment survivorship can be particularly challenging. The purpose of this study is to describe the health-related quality of life (HRQL) and psychological adaptation of YAs after treatment, relative to young adults without cancer. METHODS: Three cohorts of YAs of mixed cancer diagnoses (N = 120, 0-12 months after treatment; N = 102, 13-24 months after treatment; and N = 113, 25-60 months after treatment; combined M = 31.8 years old, combined sex = 68% women) and an age-, education-, sex-, and partner status-matched group of healthy control participants (HCs; N = 335) were recruited via an online research panel. All participants completed measures assessing demographic and clinical characteristics, HRQL (physical, emotional, social, and spiritual), and psychological adaptation (anxiety, depression, positive affect, posttraumatic growth). Measure content was slightly modified for applicability to HCs without a cancer history. RESULTS: Multivariate analysis of covariance found a significant main effect for group (YAs versus HCs) and a significant group-by-cohort interaction. YAs reported poorer physical (P = .005, d = .22) and emotional well-being (P = .011, d = .20) but better social well-being (P < .001, d = .49). YAs reported comparatively stable scores (P = .74) for posttraumatic growth compared to HCs, who reported greater posttraumatic growth across cohorts (P = .01, d = 16). CONCLUSIONS: Findings underscore the negative and positive sequelae for YAs and highlight the need for comprehensive assessment among YA survivors of cancer. A matched, HC group allows the HRQL and psychological adaptation of YAs to be placed in context, enabling a more precise determination of the impact of cancer on YAs.

Symptom burden among young adults with breast or colorectal cancer.

BACKGROUND: Cancer incidence has increased among young adults (YAs) and survival rates have not improved compared with other age groups. Patient-reported outcomes may enhance our understanding of this vulnerable population. METHODS: In a multisite prospective study, patients completed a cancer symptom inventory at the time of enrollment (T1) and 4 weeks to 5 weeks later (T2). YAs (those aged ≤ 39 years) with breast or colorectal cancer were compared with older adults (those aged ≥ 40 years) with breast or colorectal cancer with regard to symptom severity, symptom interference, changes over time, and medical care. RESULTS: Participants included 1544 patients with breast cancer (96 of whom were YAs) and 718 patients with colorectal cancer (37 of whom were YAs). Compared with older adults, YAs with breast cancer were more likely to report moderate/severe drowsiness, hair loss, and symptom interference with relationships at T1. YAs with colorectal cancer were more likely to report moderate/severe pain, fatigue, nausea, distress, drowsiness, shortness of breath, and rash plus interference in general activity, mood, work, relationships, and life enjoyment compared with older adults. Compared with older adults, shortness of breath, appetite, and sore mouth were more likely to improve in YAs with breast cancer; vomiting was less likely to improve in YAs with colorectal cancer. Referrals for supportive care were few, especially among patients with colorectal cancer. YAs with breast cancer were somewhat more likely to be referred to nutrition and psychiatry services than older patients. CONCLUSIONS: YAs reported symptom severity, symptom interference, and variations over time that were distinct from older patients. Distinctions were found to differ by diagnostic group. These findings enhance the understanding of symptom burden in YAs and inform the development of targeted interventions and future research.

Prospective longitudinal evaluation of a symptom cluster in breast cancer.

CONTEXT: Symptom cluster research expands cancer investigations beyond a focus on individual symptoms in isolation. OBJECTIVES: We conducted a prospective longitudinal study of sleep, fatigue, depression, anxiety, and perceived cognitive impairment in patients with breast cancer undergoing chemotherapy. METHODS: Patient-reported outcome measures were administered prior to chemotherapy, at Cycle 4 Day 1, and six months after initiating chemotherapy. Participants were divided into four groups and assigned a symptom cluster index (SCI) score based on the number/severity of symptoms reported at enrollment. RESULTS: Participants (N = 80) were mostly women (97.5%) with Stage II (69.0%) breast cancer, 29-71 years of age. Scores on all measures were moderately-highly correlated across all time points. There were time effects for all symptoms, except sleep quality (nonsignificant trend), with most symptoms worsening during chemotherapy, although anxiety improved. There were no significant group × time interactions; all four SCI groups showed a similar trajectory of symptoms over time. Worse performance status and quality of life were associated with higher SCI score over time. CONCLUSION: With the exception of anxiety, the coherence of the symptom cluster was supported by similar patterns of severity and change over time in these symptoms (trend for sleep quality). Participants with higher SCI scores prior to chemotherapy continued to experience greater symptom burden during and after chemotherapy. Early assessment and intervention addressing this symptom cluster (vs. individual symptoms) may have a greater impact on patient performance status and quality of life for patients with higher SCIs.

Square Pegs, Round Hole? Ensuring Fit in the AYAO Spectrum for Adolescents and Young Adults with Genetic Risk for Cancer.

This paper presents a case example of a young woman at genetic risk for future cancer. We discuss psychosocial challenges that adolescents and young adults (AYAs) may share with their cancer survivor peers, and describe an example of psychosocial care. A scientific foundation denoting the needs of AYAs at risk for heritable cancers is lacking, and it is unknown if these AYAs receive adequate support services. This is a call to action for practitioners and researchers to engage in initiatives that assure these AYAs have access to valuable support and more clearly mark their place within the spectrum of AYA oncology.

Longitudinal prospective assessment of sleep quality: before, during, and after adjuvant chemotherapy for breast cancer.

PURPOSE: Cross-sectional data suggest that many individuals with breast cancer experience significant sleep disturbance across the continuum of care. Understanding the longitudinal trajectory of sleep disturbance may help identify factors associated with its onset, severity, or influence on health-related quality of life (HRQL). Study objectives were to observe sleep quality in breast cancer patients prior to, during, and after completion of adjuvant chemotherapy, evaluate its relationship with HRQL and explore correlates over time. METHODS: Participants were administered patient-reported outcome measures including the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy--General (FACT-G), which assesses HRQL. Data were collected prospectively 3-14 days prior to beginning chemotherapy, cycle 4 day 1 of chemotherapy, and 6 months following initiation of chemotherapy. RESULTS: Participants (n = 80) were primarily women (97.5 %) with stage II (69.0 %) breast cancer. Total FACT-G scores were negatively correlated with global PSQI scores at each time point (rho = -0.46, -0.41, -0.45; all p < 0.001). Poor sleep quality (PSQI ≥ 5) was prevalent at all time points (48.5-65.8 %); however, there were no significant changes within participants over time. Correlates with sleep quality varied across time points. Participants with poor sleep quality reported worse overall HRQL, fatigue, depression, and vasomotor/endocrine symptoms. CONCLUSIONS: These findings suggest that early identification of sleep disturbance and ongoing assessment and treatment of contributing factors over the course of care may minimize symptom burden associated with chemotherapy and prevent chronic insomnia in survivorship.

Project onward: an innovative e-health intervention for cancer survivors.

OBJECTIVE: This study examined the feasibility and acceptability of an Individual Internet Intervention (III) embedded and integrated into an Internet Support Group (ISG) with the ultimate goal of enhancing adherence and learning, compared with an individual internet invention alone. METHOD: Thirty-one posttreatment cancer survivors were randomized in groups of seven to nine to either the 8-week III + ISG intervention or the 8-week III condition. Seventeen participants met the Hospital Anxiety and Depression Scale (HADS) criteria for depressive symptoms (HADS ≥ 8). RESULTS: Among all participants, the mean number of logins over 8 weeks was 20.8 ± 17.7 logins for the III + ISG compared with 12.5 ± 12.5 in III-only (p = 0.15). Two participants in the III + ISG dropped out, compared with five in III (p = 0.39). Among the 17 participants with depressive symptoms at baseline, both the Onward and the III-only condition showed large reductions in the depression scale of HADS (d = 1.27 and 0.89, respectively). Improvement over time and time x treatment effects only reached trend significance levels (ps = 0.07 & 0.12) as this pilot was not powered to detect these differences. CONCLUSION: Both the III + ISG and III-only demonstrated pre-post reductions in depressive symptoms and high rates of utilization compared with other web-based treatments for depression. Although it is premature to make any determination as to the efficacy of the interventions tested in this feasibility study, these results indicate that pursuing the III + ISG model, as well as standard IIIs, may be fruitful areas of future research.