SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

SARS-CoV-2 acquisition and immune pathogenesis among school-aged learners in four diverse schools.

BACKGROUND: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely. METHODS: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.1 (sd); 7-17 y.o.] at four diverse schools with either remote or on-site learning. Schools A and B served low-income Hispanic learners; school C served many special-needs learners, and all provided predominantly remote instruction. School D served middle- and upper-income learners, with predominantly on-site instruction. Testing occurred in the fall (2020), and 6-8 weeks later during the fall-winter surge (notable for a tenfold increase in COVID-19 cases). Immune responses and mitigation fidelity were also measured. RESULTS: We found SARS-CoV-2 infections in 17 learners only during the surge. School A (97% remote learners) had the highest infection (10/70, 14.3%, p < 0.01) and IgG positivity rates (13/66, 19.7%). School D (93% on-site learners) had the lowest infection and IgG positivity rates (1/63, 1.6%). Mitigation compliance [physical distancing (mean 87.4%) and face-covering (91.3%)] was remarkably high at all schools. Documented SARS-CoV-2-infected learners had neutralizing antibodies (94.7%), robust IFN-γ + T cell responses, and reduced monocytes. CONCLUSIONS: Schools can implement successful mitigation strategies across a wide range of student diversity. Despite asymptomatic to mild SARS-CoV-2 infection, children generate robust humoral and cellular immune responses. IMPACT: Successful COVID-19 mitigation was implemented across a diverse range of schools. School-associated SARS-CoV-2 infections reflect regional rates rather than remote or on-site learning. Seropositive school-aged children with asymptomatic to mild SARS-CoV-2 infections generate robust humoral and cellular immunity.

Exploration of Barriers and Facilitators to Implementing Best Practice in Exercise Medicine in Primary Pediatric Care-Pediatrician Perspectives.

PURPOSE: Despite the known health benefits of physical activity (PA), few primary care pediatricians discuss, evaluate, or prescribe PA for children. The goal of this study was to examine pediatricians' thoughts and practices related to child PA and the perceived facilitators and barriers to implementing PA evaluation and prescription in pediatric primary care clinics. METHODS: The Consolidated Framework for Implementation Research was used to explore implementation barriers and facilitators. A mixed-method design combined questionnaires and focus groups with 27 pediatricians. RESULTS: Despite the pediatricians' beliefs that PA is important for patients, there was wide practice variability in their approaches to discussing PA. Several perceived barriers to implementing PA evaluation and prescription were identified, including lack of knowledge and training, managing time for PA with multiple demands, the need for a team approach and simple PA tools and resources, support for patient tailoring of PA messaging, and a need for PA best practice champions. CONCLUSION: The identified barriers to implementing evidence in PA suggest several directions for improvement, including a care-team approach; quick, inexpensive, and simple PA tools; community PA partnerships; PA training in medical education; evidence-based strategies; and PA directories for families. These efforts could facilitate the implementation of PA best practices in pediatrics.

Exercise-associated prevention of adult cardiovascular disease in children and adolescents: monocytes, molecular mechanisms, and a call for discovery.

Atherosclerosis originates in childhood and adolescence. The goal of this review is to highlight how exercise and physical activity during childhood and adolescence, critical periods of growth and development, can prevent adult cardiovascular disease (CVD), particularly through molecular mechanisms of monocytes, a key cell of the innate immune system. Monocytes are heterogeneous and pluripotential cells that can, paradoxically, play a role in both the instigation and prevention of atherosclerosis. Recent discoveries in young adults reveal that brief exercise affects monocyte gene pathways promoting a cell phenotype that patrols the vascular system and repairs injuries. Concurrently, exercise inhibits pro-inflammatory monocytes, cells that contribute to vascular damage and plaque formation. Because CVD is typically asymptomatic in youth, minimally invasive techniques must be honed to study the subtle anatomic and physiologic evidence of vascular dysfunction. Exercise gas exchange and heart rate measures can be combined with ultrasound assessments of vascular anatomy and reactivity, and near-infrared spectroscopy to quantify impaired O2 transport that is often hidden at rest. Combined with functional, transcriptomic, and epigenetic monocyte expression and measures of monocyte-endothelium interaction, molecular mechanisms of early CVD can be formulated, and then translated into effective physical activity-based strategies in youth to prevent adult-onset CVD.

Body composition and neuromotor development in the year after NICU discharge in premature infants.

BACKGROUND: Hypothesis: neuromotor development correlates to body composition over the first year of life in prematurely born infants and can be influenced by enhancing motor activity. METHODS: Forty-six female and 53 male infants [27 ± 1.8 (sd) weeks] randomized to comparison or exercise group (caregiver provided 15-20 min daily of developmentally appropriate motor activities) completed the year-long study. Body composition [lean body and fat mass (LBM, FM)], growth/inflammation predictive biomarkers, and Alberta Infant Motor Scale (AIMS) were assessed. RESULTS: AIMS at 1 year correlated with LBM (r = 0.32, p < 0.001) in the whole cohort. However, there was no effect of the intervention. LBM increased by ~3685 g (p < 0.001)); insulin-like growth factor-1 (IGF-1) was correlated with LBM (r = 0.36, p = 0.002). IL-1RA (an inflammatory biomarker) decreased (-75%, p < 0.0125). LBM and bone mineral density were significantly lower and IGF-1 higher in the females at 1 year. CONCLUSIONS: We found an association between neuromotor development and LBM suggesting that motor activity may influence LBM. Our particular intervention was ineffective. Whether activities provided largely by caregivers to enhance motor activity in prematurely born infants can affect the interrelated (1) balance of growth and inflammation mediators, (2) neuromotor development, (3) sexual dimorphism, and/or (4) body composition early in life remains unknown.

A new approach to estimate aerobic fitness using the NHANES dataset.

INTRODUCTION: Physical activity and fitness are essential for healthy growth in children. The National Health and Nutrition Examination Survey (NHANES) evaluated fitness by estimating V̇O2 max from submaximal measurements of heart rate (HR) during graded treadmill exercise. Our aims were (a) to examine how well NHANES methodology used to estimate V̇O2 max correlated with actual VO2 max and (b) to evaluate a novel fitness metric using actual data collected during exercise and its relationship to physical activity and sedentary time, lipid profiles, and body composition. METHODS: Fifty-three adolescents completed NHANES submaximal exercise protocol and maximal graded cardiopulmonary exercise testing. We used a novel approach to quantifying fitness (Δvelocity × incline × body mass (VIM)/ΔHR slopes) and evaluated its relationship to physical activity and sedentary time using NHANES data (n = 4498). In a subset (n = 740), we compared ΔVIM/ΔHR slopes to NHANES estimated V̇O2 max and examined their relationship to cardiovascular risk factors (BMI percentiles and lipid levels). RESULTS: Measured V̇O2 peak was moderately correlated with NHANES estimated V̇O2 max (r = 0.53, P < 0.01). Significantly higher ΔVIM/ΔHR slopes were associated with increased physical activity and decreased sedentary time. ΔVIM/ΔHR slopes were negatively associated with LDL, triglycerides, and BMI percentiles (P < 0.01). In general, the two fitness models were similar; however, ΔVIM/ΔHR was more discriminating than NHANES in quantifying the relationship between fitness and LDL levels. CONCLUSION: We found that the NHANES estimated V̇O2 max accounted for approximately 28% of the variability in the measured V̇O2 peak. Our approach to estimating fitness (ΔVIM/ΔHR slopes) using actual data provided similar relationships to lipid levels. We suggest that fitness measurements based on actually measured data may produce more accurate assessments of fitness and, ultimately, better approaches linking exercise to health in children.

Exercise Science and Child Health: A Tale of Many Journeys.

Children are the most naturally physically active human beings; reduced physical activity is a cardinal sign of childhood disease, and exercise testing provides mechanistic insights into health and disease that are often hidden when the child is at rest. The physical inactivity epidemic is leading to increased disease risk in children and, eventually, in adults in unprecedented ways. Cardiopulmonary exercise testing (CPET) biomarkers are used to assess disease severity, progress, and response to therapy across an expanding range of childhood diseases and conditions. There is mounting data that fitness in children tracks across the life span and may prove to be an early, modifiable indicator of cardiovascular disease risk later in life. Despite these factors, CPET has failed to fulfill its promise in child health research and clinical practice. A major barrier to more accurate and effective clinical use of CPET in children is that data analytics and testing protocols have failed to keep pace with enabling technologies and computing capacity. As a consequence, biomarkers of fitness and physical activity have yet to be widely incorporated into translational research and clinical practice in child health. In this review, the author re-examines some of the long-held assumptions that mold CPET in children. In particular, the author suggests that current testing strategies that rely predominantly on maximal exercise may, inadvertently, obfuscate novel and clinically useful insights that can be gleaned from more comprehensive data analytics. New pathways to discovery may emanate from the simple recognition that the physiological journey that human beings undertake in response to the challenge of exercise may be far more important than the elusive destination of maximal or peak effort.

Inter- and intra-subject variability of nitric oxide levels in leukocyte subpopulations.

Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes. We measured NO levels using the fluorescent probe, diaminofluorescein (DAF-2DA), and flow cytometry in monocytes, neutrophils, and natural killer cells from healthy subjects immediately after blood draw (Time 0) and 30, 60, and 120 min following the blood draw. There was no significant difference among the 4 study time points in NO (DAF-2) levels, though there was wide intra-subject variability at all time points. Using LPS stimulation, we compared iNOS (the more traditional surrogate marker of NO dynamics) with NO (by DAF-2) in natural killer cells and monocytes and, we found no difference in the response patterns. In summary, we did find that within a 2-hour interval from blood draw to sample processing, there was a remarkably wide intra-subject variability in expression of intracellular NO (DAF-2) in leukocytes of healthy individuals at baseline and over time. The mechanism(s) for these differences are not known but could clearly confound efforts to detect changes in NO metabolism in white blood cells. We speculate that rapid pulsatility of NO could explain the wide variability seen.

Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise.

BackgroundPoor aerobic fitness is associated with worsening of asthma symptoms, and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes, reflecting a reduced responsiveness to stress.MethodsIn a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to an acute exercise challenge before and after the exercise training intervention. Peripheral blood mononuclear cell (PBMC) gene expression of GR, GRß, HSP70, TGFß1, and TGFß2 was determined using reverse-transcriptase PCR (RT-PCR).ResultsPeak VO2 increased by 14.6±2.3%, indicating an effective training (P<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the exercise training intervention, there was a significant decrease in baseline GR expression (P<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents.ConclusionsThis is the first study in adolescents to show that exercise training reduces GR expression in circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health.

Association between supraclavicular brown adipose tissue composition at birth and adiposity gain from birth to 6 months of age.

BackgroundBrown adipose tissue (BAT) is associated with higher energy expenditure and lower adiposity in adults. However, the relationship between BAT composition and adiposity in early life is unknown. The objective of this study was to test the hypothesis that brown fat composition at birth is prospectively associated with adiposity gain during the first 6 months of postnatal life.MethodsN=35 healthy infants were followed up prospectively from intrauterine life and birth through 6 months of age. Dixon magnetic resonance imaging (MRI) scans were conducted during the neonatal period to characterize supraclavicular BAT composition. Dual-energy X-ray absorptiometry to assess total body composition was performed within the first and sixth months of life.ResultsAfter adjusting for potential confounding factors, a more brown-like composition (smaller fat fraction) of the supraclavicular BAT depot was associated with a smaller increase in percent body fat over the first 6 months of postnatal life.ConclusionsA more brown-like BAT composition at birth appears to be protective against excess adiposity gain in early life. Newborn BAT tissue may constitute a target for prevention strategies against the subsequent development of obesity.

Assessing Parent Perceptions of Physical Activity in Families of Toddlers With Neurodevelopmental Disorders: The Parent Perceptions of Physical Activity Scale (PPPAS).

PURPOSE: The purpose of this study was to examine a new tool (PPPAS = Parent Perceptions of Physical Activity Scale-Preschool) developed to study parental perceptions of physical activity (PA) among parents of toddler and preschool age children. METHOD: 143 children (mean age 31.65 months; 75% male) and their parents were recruited from a neurodevelopmental clinic. Parents completed questionnaires, and both a psychologist and a physician evaluated the children. Eighty-three percent of the children received a diagnosis of Autism Spectrum Disorder; 20% of the children had a BMI > 85th percentile. Analyses were conducted to evaluate the reliability, concurrent validity, discriminant validity, and predictive validity of PPPAS scores. RESULTS: Results supported a two-factor structure: Perceptions of the Benefits of PA and the Barriers to PA. The internal consistency of scores was good for both PPPAS subscales, derived from the two factors. Parent perceptions of barriers to PA were significantly correlated with delays in overall adaptive functioning, daily living skills, socialization, and motor skills. When a child's motor skills were delayed, parents were less likely to believe PA was beneficial and perceived more barriers to PA. Parent perceptions of barriers to PA predicted parent-reported weekly unstructured PA and ratings of how physically active their child was compared with other children. CONCLUSION: We present the PPPAS-Preschool for use in pediatric exercise research and discuss potential applications for the study of parent perceptions of PA in young children.

Professional and political reflections on the 'grand round': a critical case study.

This case study presents a critical reflective account of a change to working practices in one NHS Trust. To promote quality care and effective clinical decision making, a 'grand round' was introduced in the orthopaedic department. Implementation presented frustrations and challenges for members of the multidisciplinary team. These are explored using transformative learning and critical reflection, enabling connections to be made between micro-level interactions of clinical care and macro-level structures that frame healthcare services. It is important that nurses recognise the escalating impact of a neoliberal agenda, and new public management, that drive UK health policy and politics. The value base of nursing is threatened by a corporate culture that measures performance in terms of institutional targets rather than individual care.

Sex Differences in the Relationship between Fitness and Obesity on Risk for Asthma in Adolescents.

OBJECTIVE: To evaluate the relationship of fitness and obesity on asthma risk in adolescent girls and boys. STUDY DESIGN: A cross-sectional assessment of participants 12-19 years of age was conducted by the use of data from the 1999-2004 National Health and Nutrition Examination Survey. Participants completed cardiorespiratory fitness testing, body composition measurements, and respiratory questionnaires. RESULTS: A total of 4828 participants were included. Overweight/obesity was associated with increased odds of history of asthma (aOR 1.63, 95% CI 1.16-2.30), current asthma (aOR 1.73, 95% CI 1.13, 2.64), and wheezing (aOR 1.40, 95% CI 1.03-1.91) in girls. Overweight/obesity also was associated with increased odds of asthma attacks (aOR 2.67, 95% CI 1.56-4.65) and wheezing related to exercise (aOR 1.60, 95% CI 1.07-2.38) in girls. High fitness was associated with lower odds of asthma-related visits to the emergency department (aOR 0.24, 95% CI 0.07-0.89), wheezing-related medical visits (aOR 0.31, 95% CI 0.13-0.75), wheezing-related missed days (aOR 0.14, 95% CI 0.06-0.33), and wheezing related to exercise (aOR 0.43, 95% CI 0.24-0.76) in boys. CONCLUSION: Overweight/obesity is associated with increased asthma prevalence and morbidity in girls but not in boys, independent of fitness. High fitness is associated with decreased rates of asthma morbidity in boys but not in girls, independent of weight status. Obesity and fitness may each influence asthma onset and severity in different ways for girls compared with boys.

Bridging the Gaps: the Promise of Omics Studies in Pediatric Exercise Research.

In this review, we highlight promising new discoveries that may generate useful and clinically relevant insights into the mechanisms that link exercise with growth during critical periods of development. Growth in childhood and adolescence is unique among mammals and is a dynamic process regulated by an evolution of hormonal and inflammatory mediators, age-dependent progression of gene expression, and environmentally modulated epigenetic mechanisms. Many of these same processes likely affect molecular transducers of physical activity. How the molecular signaling associated with growth is synchronized with signaling associated with exercise is poorly understood. Recent advances in "omics"-namely genomics and epigenetics, metabolomics, and proteomics-now provide exciting approaches and tools that can be used for the first time to address this gap. A biologic definition of "healthy" exercise that links the metabolic transducers of physical activity with parallel processes that regulate growth will transform health policy and guidelines that promote optimal use of physical activity.

Cardiopulmonary Exercise Testing in Children and Adolescents with High Body Mass Index.

Consensus has yet to be achieved on whether obesity is inexorably tied to poor fitness. We tested the hypothesis that appropriate reference of cardiopulmonary exercise testing (CPET) variables to lean body mass (LBM) would eliminate differences in fitness between high-BMI (≥ 95th percentile, n = 72, 50% female) and normal-BMI (< 85th percentile, n = 142, 49% female), otherwise-healthy children and adolescents typically seen when referencing body weight. We measured body composition with dual x-ray absorptiometry (DXA) and CPET variables from cycle ergometry using both peak values and submaximal exercise slopes (peak VO2, ΔVO2/ΔHR, ΔWR/ΔHR, ΔVO2/ΔWR, and ΔVE/ΔVCO2). In contrast to our hypothesis, referencing to LBM tended to lessen, but did not eliminate, the differences (peak VO2 [p < .004] and ΔVO2/ΔHR [p < .02]) in males and females; ΔWR/ΔHR differed between the two groups in females (p = .041) but not males (p = .1). The mean percent predicted values for all CPET variables were below 100% in the high-BMI group. The pattern of CPET abnormalities suggested a pervasive impairment of O2 delivery in the high-BMI group (ΔVO2/ΔWR was in fact highest in normal-BMI males). Tailoring lifestyle interventions to the specific fitness capabilities of each child (personalized exercise medicine) may be one of the ways to stem what has been an intractable epidemic.

Cerebral and Muscle Tissue Oxygenation During Incremental Cycling in Male Adolescents Measured by Time-Resolved Near-Infrared Spectroscopy.

Near-infrared spectroscopy has long been used to measure tissue-specific O2 dynamics in exercise, but most published data have used continuous wave devices incapable of quantifying absolute Hemoglobin (Hb) concentrations. We used time-resolved near-infrared spectroscopy to study exercising muscle (Vastus Lateralis, VL) and prefrontal cortex (PFC) Hb oxygenation in 11 young males (15.3 ± 2.1 yrs) performing incremental cycling until exhaustion (peak VO2 = 42.7 ± 6.1 ml/min/kg, mean peak power = 181 ± 38 W). Time-resolved near-infrared spectroscopy measurements of reduced scattering (µs´) and absorption (µa) at three wavelengths (759, 796, and 833 nm) were used to calculate concentrations of oxyHb ([HbO2]), deoxy Hb ([HbR]), total Hb ([THb]), and O2 saturation (stO2). In PFC, significant increases were observed in both [HbO2] and [HbR] during intense exercise. PFC stO2% remained stable until 80% of total exercise time, then dropped (-2.95%, p = .0064). In VL, stO2% decreased until peak time (-6.8%, p = .01). Segmented linear regression identified thresholds for PFC [HbO2], [HbR], VL [THb]. There was a strong correlation between timing of second ventilatory threshold and decline in PFC [HbO2] (r = .84). These findings show that time-resolved near-infrared spectroscopy can be used to study physiological threshold phenomena in children during maximal exercise, providing insight into tissue specific hemodynamics and metabolism.

Obesity, Asthma, and Exercise in Child and Adolescent Health.

Obesity increases the risk of asthma throughout life but the underlying mechanisms linking these all too common threats to child health are poorly understood. Acute bouts of exercise, aerobic fitness, and levels of physical activity clearly play a role in the pathogenesis and/or management of both childhood obesity and asthma. Moreover, both obesity and physical inactivity are associated with asthma symptomatology and response to therapy (a particularly challenging feature of obesity-related asthma). In this article, we review current understandings of the link between physical activity, aerobic fitness and the asthma-obesity link in children and adolescents (e.g., the impact of chronic low-grade inflammation, lung mechanics, and direct effects of metabolic health on the lung). Gaps in our knowledge regarding the physiological mechanisms linking asthma, obesity and exercise are often compounded by imprecise estimations of adiposity and challenges of assessing aerobic fitness in children. Addressing these gaps could lead to practical interventions and clinical approaches that could mitigate the profound health care crisis of the increasing comorbidity of asthma, physical inactivity, and obesity in children.

The psychosocial experiences of older palliative patients while participating in a Living with Hope Program.

OBJECTIVE: Several studies have reported the effectiveness of a variety of psychosocial interventions in increasing levels of hope in palliative care patients. The experience of palliative patients while participating in these interventions is unknown. Understanding these experiences would provide a rich understanding of how the interventions work to foster hope. The purpose of the present study was to describe the psychosocial processes that participants with advanced cancer receiving palliative care experienced when taking part in a Living with Hope Program (LWHP). METHOD: In the context of a study evaluating the LWHP, data were collected from 13 dyads (persons with advanced cancer and their caregivers) at two timepoints (one week apart). A thematic qualitative analysis of 52 open-ended audiotaped interviews was conducted that focused on the psychosocial processes that occurred during the LWHP. RESULTS: The average age of palliative participants was 67 (SD = 6.6) and of their family caregivers 61 years of age (SD = 13.9). A thematic analysis suggested that the participants experienced the following psychosocial processes while participating in the LWHP: (1) reminiscing, (2) leaving a legacy, (3) positive reappraisal, and (4) motivational processes. These processes are the mechanisms by which the LWHP fosters the positive outcomes of increasing hope and improving quality of life. As well, the finding of motivational processes suggested that the LWHP may also increase life satisfaction, which is an outcome of motivational processes. Significance of the results: The findings from our study underscore the importance of uncovering the psychosocial processes through which the LWHP works to foster hope. They will assist in making revisions to the intervention that will increase its effectiveness, as well as providing a better understanding of hope in persons with advanced cancer.