Identification and characterization of calreticulin as a novel plasminogen receptor.

Calreticulin (CRT) was originally identified as a key calcium-binding protein of the endoplasmic reticulum. Subsequently, CRT was shown to possess multiple intracellular functions, including roles in calcium homeostasis and protein folding. Recently, several extracellular functions have been identified for CRT, including roles in cancer cell invasion and phagocytosis of apoptotic and cancer cells by macrophages. In the current report, we uncover a novel function for extracellular CRT and report that CRT functions as a plasminogen-binding receptor that regulates the conversion of plasminogen to plasmin. We show that human recombinant or bovine tissue-derived CRT dramatically stimulated the conversion of plasminogen to plasmin by tissue plasminogen activator or urokinase-type plasminogen activator. Surface plasmon resonance analysis revealed that CRT-bound plasminogen (KD = 1.8 µM) with moderate affinity. Plasminogen binding and activation by CRT were inhibited by ε-aminocaproic acid, suggesting that an internal lysine residue of CRT interacts with plasminogen. We subsequently show that clinically relevant CRT variants (lacking four or eight lysines in carboxyl-terminal region) exhibited decreased plasminogen activation. Furthermore, CRT-deficient fibroblasts generated 90% less plasmin and CRT-depleted MDA MB 231 cells also demonstrated a significant reduction in plasmin generation. Moreover, treatment of fibroblasts with mitoxantrone dramatically stimulated plasmin generation by WT but not CRT-deficient fibroblasts. Our results suggest that CRT is an important cellular plasminogen regulatory protein. Given that CRT can empower cells with plasmin proteolytic activity, this discovery may provide new mechanistic insight into the established role of CRT in cancer.

Patient and Parent Characteristics Related to Quality of Life and Self-Esteem in Healthy Youth Undergoing Provocative Growth Hormone Testing.

OBJECTIVE: To examine how height and youth as well as parenting characteristics associate with quality of life (QoL) and self-esteem among healthy youth undergoing growth evaluation with growth hormone (GH) testing. STUDY DESIGN: Healthy youth, aged 8-14 years, undergoing provocative GH testing, and a parent completed surveys at or around the time of testing. Surveys collected demographic data; youth and parent reports of youth health-related QoL; youth reports of self-esteem, coping skills, social support, and parental autonomy support; and parent reports of perceived environmental threats and achievement goals for their child. Clinical data were extracted from electronic health records. Univariate models and multivariable linear regressions were used to identify factors associated with QoL and self-esteem. RESULTS: Sixty youth (mean height z score -2.18 ± 0.61) and their parents participated. On multivariable modeling, youth perceptions of their physical QoL associated with higher grade in school, greater friend and classmate support, and older parent age; youth psychosocial QoL with greater friend and classmate support, and with less disengaged coping; and youth height-related QoL and parental perceptions of youth psychosocial QoL with greater classmate support. Youth self-esteem associated with greater classmate support and taller mid-parental height. Youth height was not associated with QoL or self-esteem outcomes in multivariable regression. CONCLUSIONS: Perceived social support and coping skills, rather than height, were related to QoL and self-esteem in healthy short youth and may serve as an important potential area for clinical intervention.

Establishing a global regulatory floor for children's decisions about participation in clinical research.

BACKGROUND: Enrolling children in clinical trials typically requires parental or guardian permission and, when appropriate, child assent. Aligning requirements across jurisdictions would facilitate multisite pediatric trials. Guidance from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is the best candidate for a global standard but would benefit from additional specification. METHODS: Ethical analysis of ICH guidance for permission and assent for pediatric trials, with recommendations for clarification. RESULTS: ICH guidance regarding permission and assent would be enhanced by additional detail in the following areas: (1) what information should be provided to parents, guardians, and children considering a trial, and how that information should be provided; (2) the definition of "assent," the criteria for when assent should be required, and the need to include children in discussions even when assent is not mandated; (3) criteria for requiring children's signatures indicating agreement; (4) greater specificity regarding children's right to decline or withdraw; and (5) clarification of when children's wish to decline or withdraw from participation may be overridden and of what the overriding process should entail. CONCLUSION: ICH guidance provides a global standard for decision making regarding children's participation in trials. Several clarifications would facilitate the conduct of multinational pediatric research. IMPACT: Enrolling children in clinical trials requires the permission of a parent/guardian ± the assent of the minor. Differing global regulatory requirements for enrolling children complicate the conduct of multicenter and multinational trials. The authors identify points of ambiguity and/or contradiction in the International Council for Harmonization guidelines and offer recommendations for a common ethical platform for conducting global pediatric research.

Views on Short Stature of Female vs Male Endocrine Pediatric Patients Undergoing Provocative Growth Hormone Testing and Their Parents.

OBJECTIVE: Boys outnumber girls in short stature evaluations and growth hormone treatment despite absence of gender differences in short stature prevalence. Family views on short stature influence medical management, but gender-based analysis of these views is lacking. This study explored endocrine patients' and their parents' perceptions of short stature and its impact on quality of life by patient gender. METHODS: Patients aged 8 to 14 years undergoing provocative growth hormone testing and 1 parent each completed semistructured interviews. Clinical data were extracted by chart review. RESULTS: Twenty-four patient-parent dyads (6 female patients, 22 mothers; predominantly non-Hispanic White) participated. Six major themes emerged: (1) patients' perceptions of their short stature were similar by gender, (2) physical experiences of short stature were similar by gender, (3) social experiences of short stature were both similar and different by gender, (4) parental perceptions of short stature as a factor limiting their child's functionality were similar by gender, (5) concern about societal stigma related to short stature arose for both genders, and (6) patients' perceptions of parental messaging about the import of their short stature were similar by gender. CONCLUSION: Our data reveal more similarities than differences between genders in patient perceptions and patient and parent-reported experiences of short stature. Worry about stature-related stigma was noted for patients of both genders. Parental messaging about short stature emerged as an important area to explore further by patient gender. Our findings suggest that clinicians should be wary of making gender or stigma-based assumptions when evaluating children with short stature.

Perspectives on Remote Glucose Monitoring in Youth With Type 1 Diabetes.

OBJECTIVE: Continuous glucose monitoring (CGM) has become increasingly popular among youth with type 1 diabetes (T1D). Used with CGM, remote monitoring (RM) gives caregivers real-time access to patients' glucose values. Whereas RM may safeguard against hypo- and hyperglycemic events, little is known about how older children and adolescents, who are striving for independence, and their parents view the RM aspect of CGM. The goal of this study was to describe and explore parent and youth perceptions of RM. METHODS: Youth with T1D and their parents participated separately in semi-structured interviews 2 months after starting CGM. Questions focused on decisions to use and experiences with RM. RESULTS: Analysis of 43 parents and 41 youth (13.79 years ± 2.82) interviews revealed four themes, with 10 subthemes. Seven subthemes emerged in parent and youth interviews, and three emerged exclusively in parent interviews. The overarching themes included the impact of RM on (1) peace-of-mind, (2) parental anxiety, (3) communication; and addressed (4) technological limitations that prevented some from using RM. Regardless of youth age, youth and parents found comfort in parental knowledge of glucose values and parental abilities to assist youth (e.g., giving reminders to eat). Whereas RM could lead to conflicts due to excessive communication (e.g., texting), conflicts could be resolved through iterative parent-youth conversations. CONCLUSION: RM may facilitate youth independence by providing a way for them to stay connected to their support system while acquiring developmentally appropriate skills. However, families should have iterative discussions about boundaries to mitigate parental over-involvement.

Feasibility and Acceptability of a Novel Primary Care-Based Intervention to Promote Parent-Teen Communication About Teen Strengths.

Strength-based approaches to youth development have been tested in community settings and are related to improvements in social, health, and academic realms. However, little is known about similar approaches to enhance parent-teen communication (PTC) in pediatric primary care. The goal of this study was to test the feasibility and acceptability of an intervention to facilitate parent-teen communication about teen strengths. Intervention materials were developed based on a literature review, expert consultation, and feedback from stakeholders. The final intervention was a parent-directed booklet and a parent-teen discussion activity. At the well-adolescent visit (WAV), dyads received an orientation to the materials and were instructed to complete the discussion activity within 2 weeks of the WAV. Health Care Providers verbally endorsed the materials and instructed parents to read the booklet and complete the discussion activity with their teens. Acceptability was assessed at 2-week and 2-month follow-ups. Parent-adolescent dyads from an urban, pediatric primary care practice were enrolled with half assigned to the treatment group. Those in the treatment group (60 dyads) are the focus of this paper. Youth were 13-15 years old, 55% female, and 66% Black. Most participating parents (97%) were female. Fidelity was ≥ 88% for delivery of each of the intervention components. Fifty-four of the 60 parents in the intervention group completed the 2-week call. Of those 54 parents, 96% read the booklet and 62% found the booklet either extremely or very helpful. The majority of parents (67%) and teens (72%) reported that the discussion activity was excellent or very good. Analysis of qualitative data also provided rich insight into the participants' experiences with the intervention materials. Overall results suggest that an intervention to promote PTC about teen strengths is feasible and acceptable to parents and teens within primary care.

Efficacy of a Primary Care-Based Intervention to Promote Parent-Teen Communication and Well-Being: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of a primary care-based, parent-directed intervention on changes in parent-teen communication, parental beliefs about adolescents, parent and adolescent well-being, adolescent distress, and adolescent positive affect from baseline to 2-month follow-up. STUDY DESIGN: In this randomized controlled trial, 120 adolescents (13-15 years of age) scheduled for well visits and their parents were randomized to the strength intervention or control group. The intervention included a booklet highlighting 3 key messages about adolescence, instructions to have a discussion with their teen about each other's strengths, and clinician endorsement. Outcomes were assessed before the well visit and 2 months later. RESULTS: Adolescents were 61% female and 65% black. Parents were primarily female (97%); 72% had a 4-year degree or higher. The intervention had a positive impact on adolescent-reported open communication among adolescents with baseline low open communication scores (B = 3.55; P = .005; 95% CI, 1.07-6.03). Adolescents in the intervention group reported a decrease in distress (-1.54 vs 3.78; P = .05; partial eta squared [η2] = 0.038) and increase in positive affect (1.30 vs -3.64; P = .05; η2 = 0.04) compared with control group adolescents. The intervention did not affect parent-reported communication, parental beliefs, or adolescent well-being. Control parents demonstrated a marginal increase in well-being, whereas intervention parents did not (0.82 vs -0.18; P = .07; η2 = 0.029). CONCLUSIONS: This study highlights the potential impact of primary care-based, universal, low-intensity interventions targeting parents of adolescents on parent-teen communication and important adolescent health outcomes. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03496155.

Tailored medication adherence incentives for high-risk children with asthma: a pilot study.

Objective: While reminder-based electronic monitoring systems have shown promise in enhancing inhaled corticosteroid (ICS) adherence in select populations, more engaging strategies may be needed in families of children with high-risk asthma. This study assesses the acceptability and feasibility of gain-framed ICS adherence incentives in families of urban, minority children with frequent asthma hospitalization.Methods: We enrolled children aged 5-11 years with multiple yearly asthma hospitalizations in a 2-month, mixed methods, ICS adherence incentive pilot study. All participants received inhaler sensors and a smartphone app to track ICS use. During month 1, families received daily adherence reminders and weekly feedback, and children earned up to $1/day for complete adherence. No reminders, feedback, or incentives were provided in month 2. We assessed feasibility and acceptability using caregiver surveys and semi-structured interviews and ICS adherence using electronic monitoring data.Results: Of the 29 families approached, 20 enrolled (69%). Participants were primarily Black (95%), publicly insured (75%), and averaged 2.9 asthma hospitalizations in the prior year. Fifteen of the 16 caregivers (94%) surveyed at month 2 liked the idea of receiving adherence incentives. Mean adherence was significantly higher in month 1 compared with month 2 (80% vs. 33%, mean difference = 47%; 95% CI [33, 61], p < 0.001). Caregivers reported that their competing priorities often limited adherence, while incentives helped motivate child adherence.Conclusions: ICS adherence incentives were acceptable and feasible in a high-risk cohort of children with asthma. Future studies should assess the efficacy of adherence incentives in enhancing ICS adherence in high-risk children.

Does Self-Efficacy Mediate the Link Between Impulse Control and Diabetes Adherence?

OBJECTIVE: The goal of this study was to test the hypothesis that diabetes self-efficacy mediates the relationship between impulse control and type 1 diabetes (T1D) management from ages 8 to 18 years, using multilevel modeling. METHODS: Participants included 117 youth with T1D and their parents. Youth (aged 8-16 years at baseline) and parents were assessed 5 times over 2 years. Using a cohort sequential design, we first estimated the growth trajectory of adherence from age 8 to 18 years, then specified a multilevel mediation model using impulse control as the main predictor, diabetes self-efficacy as the mediator, and changes in adherence (both within- and between-individuals) as the outcome. RESULTS: According to youth-reported adherence only, self-efficacy partially mediated the within-person effect of impulse control on adherence. On occasions when youth reported increases in impulse control, they tended to report higher adherence, and this was, in part, due to increases in youths' perceived self-efficacy. Self-efficacy accounted for approximately 21% of the within-person relationship between impulse control and youth-reported adherence. There was no association between impulse control and adherence between-individuals. Impulse control and self-efficacy were not related to parent-reported adherence. CONCLUSION: Environments that enrich youth with confidence in their own diabetes-related abilities may benefit self-care behaviors in youth with T1D, but such increases in youths' perceived competence do not fully account for, or override, the behavioral benefits of impulse control. Efforts to improve adherence in youth with T1D will benefit from consideration of both impulse control and self-efficacy.

Medical and end-of-life decision making in adolescents' pre-heart transplant: A descriptive pilot study.

BACKGROUND: Adolescents and young adults undergoing heart transplantation experience risks of morbidity and mortality both pre- and post-transplant. To improve end-of-life care for this population, it is necessary to understand their medical and end-of-life decision-making preferences. AIM: (1) To examine adolescent/young adult decision-making involvement specific to heart transplant listing, and (2) to characterize their preferences specific to medical and end-of-life decision making. DESIGN: This cross-sectional research study utilized survey methods. Data were collected from October 2016 to March 2018. SETTING/PARTICIPANTS: Twelve adolescent and young adult patients listed for heart transplant (ages = 12-19 years) and one parent for each were enrolled at a single-center, US children's hospital. RESULTS: Consistent with their preferences, the majority of adolescent/young adult participants (82%) perceived a high level of involvement in the decision to be listed for transplant. Patient involvement in this decision was primarily by way of seeking advice or information from their parents and being asked to express their opinion from parents. Despite a preference among patients to discuss their prognosis and be involved in end-of-life decision making if seriously ill, only 42% of patients had discussed their end-of-life wishes with anyone. Few parents recounted having such discussions. Preferences regarding the timing and nature of end-of-life decision-making discussions varied. CONCLUSIONS: Although young people are involved in the decision to pursue heart transplantation, little attention is paid to involving them in discussions regarding end-of-life decision making in a manner that is consistent with individual preferences.

Assessment of caregiver expectations of physician communication in a pediatric setting.

BACKGROUND: In pediatrics, communication often occurs through an intermediary such as a caregiver. The goal of this study is to assess caregiver communication expectations and determine if meeting expectations influences caregiver satisfaction or instruction retention. METHODS: A survey study was performed at the Children's Hospital of Philadelphia. Before the visit, caregivers completed a survey on communication expectations, Caregiver Expected Kalamazoo Essential Elements Communication Checklist (Caregiver Expected KEECC). After the visit, caregivers were surveyed on their perception of physician communication (Caregiver Perceived KEECC) and satisfaction. Caregivers were contacted 1 week after the clinic visit to assess instruction retention. Meeting of caregiver expectation was calculated by the difference between Caregiver Expected and Caregiver Perceived KEECC scores. RESULTS: 112 caregivers participated in the study. There was no significant difference in Caregiver Expected KEECC versus Caregiver Perceived KEECC score (4.39 vs 4.56). Caregiver communication expectations were exceeded in 51.5% of the visits. Communication expectations were exceeded more among caregivers with at a college education (p <  0.01) and more among White caregivers (p <  0.01). The average caregiver satisfaction score with the clinic visit was 4.67. Higher satisfaction scores were observed in caregivers who had their communication expectations met or exceeded (p <  0.01). Caregivers with communication expectations exceeded had higher percentage recall of physician instructions (p <  0.01). CONCLUSIONS: Caregiver communication expectations may be influenced by demographic factors. Communication expectation affects visit outcomes including caregiver satisfaction and instruction retention. Therefore, physicians need to be cognizant of caregiver communication expectations, which can impact quality of the healthcare experience.

Daily Parent-Teen Conflict and Parent and Adolescent Well-Being: The Moderating Role of Daily and Person-Level Warmth.

In early-mid adolescence, parent-teen conflicts become more intense and parents' displays of warmth tend to decline temporarily. Daily increases of parent-teen conflict have been linked to concurrent increases in adolescent emotional distress, yet greater average levels of parental warmth are known to buffer adolescents' response to daily stressors such as interpersonal conflict. It is unclear whether daily increases in parental warmth may also function as a protective buffer that attenuates the daily association between parent-teen conflict and individuals' well-being. The present study aimed to fill an important gap in the literature by examining daily (within-person) fluctuations, and average between-person differences, in parental warmth as potential moderators of the daily association between parent-teen conflict intensity (defined here by the degree of negative emotions in parent-teen interactions) and well-being (distress, positive affect, and self-esteem) of both parents and adolescents. Data are based on daily reports from 120 parents-adolescents dyads recruited from a primary care practice in the Northeastern U.S. Almost all parents were mothers (Mage = 44.55, SD = 6.36), 61% of adolescents were female (Mage = 14.36, SD = 0.88), and 66% of dyads were African American. Multilevel modeling was used to assess the daily association between parent-teen conflict and well-being and examine daily and person-level (across-days) warmth as moderators of that association. Examining daily parental warmth as a moderator addressed whether the daily association between conflict and well-being varied as a function of when parental warmth increased or decreased within individuals (relative to individuals' own daily average). In contrast, examining person-level mean warmth as a moderator addressed whether the daily association between conflict and well-being varied as a function of who, on average, reported higher vs. lower levels of parental warmth. As expected, both parents and adolescents reported significantly lower well-being on days they experienced more conflict than usual. Daily fluctuations in parental warmth did not moderate the daily associations between conflict and well-being in parents or adolescents, indicating that the daily association did not change when parents were warmer than usual. In adolescents, the daily associations between conflict and distress, as well as conflict and positive affect, were moderated by person-mean levels of parental warmth, such that daily increases in conflict were associated with higher distress and lower positive affect (on the same day) primarily among adolescents with average or below average levels of parental warmth. Daily conflict was not associated with lower well-being among adolescents with higher-than-average levels of parental warmth. In parents, neither daily nor person-level warmth moderated the daily association between conflict and well-being, suggesting that the negative, daily association between conflict and well-being did not change as a function of parents' daily or average perceptions of warmth. These findings suggest that isolated, day-specific increases in warmth may be less protective than high, stable levels of parental warmth in mitigating the daily association between parent-teen conflict and adolescent well-being.

Controller adherence following hospital discharge in high risk children: A pilot randomized trial of text message reminders.

OBJECTIVE: To assess the feasibility of a mobile health, inhaled corticosteroid (ICS) adherence reminder intervention and to characterize adherence trajectories immediately following severe asthma exacerbation in high-risk urban children with persistent asthma. METHODS: Children aged 2-13 with persistent asthma were enrolled in this pilot randomized controlled trial during an asthma emergency department (ED) visit or hospitalization. Intervention arm participants received daily text message reminders for 30 days, and both arms received electronic sensors to measure ICS use. Primary outcomes were feasibility of sensor use and text message acceptability. Secondary outcomes included adherence to prescribed ICS regimen and 30-day adherence trajectories. Group-based trajectory modeling was used to examine adherence trajectories. RESULTS: Forty-one participants (mean age 5.9) were randomized to intervention (n = 21) or control (n = 20). Overall, 85% were Black, 88% had public insurance, and 51% of the caregivers had a high school education or less. Thirty-two participant families (78%) transmitted medication adherence data; of caregivers who completed the acceptability survey, 25 (96%) chose to receive daily reminders beyond that study interval. Secondary outcome analyses demonstrated similar average daily adherence between groups (intervention = 36%; control = 32%, P = 0.73). Three adherence trajectories were identified with none ever exceeding 80% adherence. CONCLUSIONS: Within a high-risk pediatric cohort, electronic monitoring of ICS use and adherence reminders delivered via text message were feasible for most participants, but there was no signal of effect. Adherence trajectories following severe exacerbation were suboptimal, demonstrating an important opportunity for asthma care improvement.

Decision-Making Involvement and Prediction of Adherence in Youth With Type 1 Diabetes: A Cohort Sequential Study.

Objective: To assess developmental trajectories of decision-making involvement (DMI), defined as the ways in which parents and children engage each other in decision-making about illness management, in youth with type 1 diabetes (T1D) and examine the effects of DMI on levels of and changes in adherence with age. Methods: Participants included 117 youth with T1D, enrolled at ages 8-16 years and assessed five times over 2 years. The cohort sequential design allowed for the approximation of the longitudinal curve from age 8 to 19 from overlapping cohort segments. Children and parents completed the Decision-Making Involvement Scale, which yields subscales for different aspects of DMI, and a self-report adherence questionnaire. Mixed-effects growth curve modeling was used for analysis, with longitudinal measures nested within participant and participants nested within cohort. Results: Most aspects of DMI (Parent Express, Parent Seek, Child Express, and Joint) increased with child age; scores on some child report subscales (Parent Express, Child Seek, and Joint) decreased after age 12-14 years. After accounting for age, Child Seek, Child Express, and Joint were associated with overall higher levels of adherence in both child (estimates = 0.08-0.13, p < .001) and parent (estimates = 0.07- 0.13, p < .01) report models, but they did not predict changes in adherence with age. Conclusion: These data suggest that helping children to be more proactive in T1D discussions, by encouraging them to express their opinions, share information, and solicit guidance from parents, is a potential target for interventions to enhance effective self-management.

A multivariate model exploring the predictive value of demographic, adolescent, and family factors on glycemic control in adolescents with type 1 diabetes.

OBJECTIVE: The current study examined how a comprehensive set of variables from multiple domains, including at the adolescent and family level, were predictive of glycemic control in adolescents with type 1 diabetes (T1D). METHODS: Participants included 100 adolescents with T1D ages 10-16 yrs and their parents. Participants were enrolled in a longitudinal study about youth decision-making involvement in chronic illness management of which the baseline data were available for analysis. Bivariate associations with glycemic control (HbA1C) were tested. Hierarchical linear regression was implemented to inform the predictive model. RESULTS: In bivariate analyses, race, family structure, household income, insulin regimen, adolescent-reported adherence to diabetes self-management, cognitive development, adolescent responsibility for T1D management, and parent behavior during the illness management discussion were associated with HbA1c. In the multivariate model, the only significant predictors of HbA1c were race and insulin regimen, accounting for 17% of the variance. Caucasians had better glycemic control than other racial groups. Participants using pre-mixed insulin therapy and basal-bolus insulin had worse glycemic control than those on insulin pumps. CONCLUSIONS: This study shows that despite associations of adolescent and family-level variables with glycemic control at the bivariate level, only race and insulin regimen are predictive of glycemic control in hierarchical multivariate analyses. This model offers an alternative way to examine the relationship of demographic and psychosocial factors on glycemic control in adolescents with T1D.

Problems and hopes perceived by mothers, fathers and physicians of children receiving palliative care.

BACKGROUND: The quality of shared decision making for children with serious illness may depend on whether parents and physicians share similar perceptions of problems and hopes for the child. OBJECTIVE: (i) Describe the problems and hopes reported by mothers, fathers and physicians of children receiving palliative care; (ii) examine the observed concordance between participants; (iii) examine parental perceived agreement; and (iv) examine whether parents who identified specific problems also specified corresponding hopes, or whether the problems were left 'hopeless'. METHOD: Seventy-one parents and 43 physicians were asked to report problems and hopes and perceived agreement for 50 children receiving palliative care. Problems and hopes were classified into eight domains. Observed concordance was calculated between parents and between each parent and the physicians. RESULTS: The most common problem domains were physical body (88%), quality of life (74%) and medical knowledge (48%). The most common hope domains were quality of life (88%), suffering (76%) and physical body (39%). Overall parental dyads demonstrated a high percentage of concordance (82%) regarding reported problem domains and a lower percentage of concordance on hopes (65%). Concordance between parents and physicians regarding specific children was lower on problem (65-66%) and hope domains (59-63%). Respondents who identified problems regarding a child's quality of life or suffering were likely to also report corresponding hopes in these domains (93 and 82%, respectively). CONCLUSION: Asking parents and physicians to talk about problems and hopes may provide a straightforward means to improve the quality of shared decision making for critically ill children.

Testicular tissue cryopreservation in prepubertal male children: an analysis of parental decision-making.

BACKGROUND: Infertility is an unfortunate treatment-related consequence for some pediatric malignancies as well as some non-malignant conditions treated with stem cell transplant. Unlike pubertal males, prepubertal males cannot produce semen for cryopreservation. This manuscript reports on the acceptability and safety of a multi-institutional protocol for offering testicular tissue cryopreservation to families of prepubertal male children at highest risk for infertility. Data on decision influences, decision-making control, and emotional state when considering this option are described. PROCEDURE: Prepubertal males facing gonadotoxic therapy were offered testicular cryopreservation. Post-biopsy, patients were followed for acute side effects. In addition, parents and patients were asked to complete questionnaires, whether or not they chose to cryopreserve tissue. RESULTS: Seventy-four prepubertal male children were approached. Fifty-seven families (77%) consented to the testicular biopsy; 48 of 57 underwent the procedure. There was one post-operative side effect. Parents who agreed to testicular cryopreservation and those that did not felt in control of this decision. Parents who consented to the biopsy and refusers were not deterred by the experimental nature of the protocol. An important decision-making influence was the risk of the biopsy. CONCLUSION: Biopsy and cryopreservation of testicular tissue from prepubertal male children was performed successfully and safely at three institutions. Parents faced with this option at diagnosis can make an informed decision and weigh carefully the risks and benefits. Although asked to make a decision soon after they were given a difficult diagnosis, parents uniformly felt in control of this decision.

Patient involvement in informed consent for pediatric phase I cancer research.

OBJECTIVE: To examine children's and adolescents' involvement in the informed consent conference for phase I cancer trials and test associations with patient age, ease of understanding, and pressure to participate. PROCEDURE: Participants included 61 patients aged 7 through 21 years who were offered participation in a phase I trial. Consent conferences were audiotaped, transcribed, and coded for communication between patients and physicians and between patients and parents. RESULTS: On the basis of word counts, the mean proportion of the consent conference in which the physician was talking to the patient was 36%; the vast majority (73%) of this communication consisted of giving information. Physician-patient communication increased with age, but overall levels of patient-to-physician communication were low (3%). After controlling for patient age, greater physician-to-patient communication was associated with greater ease of understanding. CONCLUSIONS: The focus on providing information in the context of informed consent may come at the expense of other communication exchanges that are important to patients, especially in the context of end-of-life decisions. Children and adolescents may benefit from the assent process when physicians direct more of their communication to them. Future research should identify the reasons for low patient communication during the consent conference and strategies to enhance their participation in decision making about phase I trial enrollment.

Stakeholders' opinions on the implementation of pediatric whole exome sequencing: implications for informed consent.

Advances in whole genome and whole exome sequencing (WGS/WES) technologies have led to increased availability in clinical settings. Currently, there are few guidelines relating to the process and content of informed consent for WGS/WES, nor to which results should be returned to families. To address this gap, we conducted focus groups to assess the views of professionals, parents, and adolescents for the future implementation of WES. The discussions assessed understanding of the risks and benefits of WES, preferences for the informed consent discussion, process for return of results, and the decision-making role of the pediatric patient. Professional focus group participants included bioethicists, physicians, laboratory directors, and genetic counselors. Parent focus groups included individuals with children who could be offered sequencing due to a potential genetic cause of the child's condition. On-line discussion groups were conducted with adolescents aged 13-17 who had a possible genetic disorder. We identified discrepancies between professionals and patient groups regarding the process and content of informed consent, preference for return of results, and the role of the child in decision-making. Professional groups were concerned with the uncertainty regarding professional obligations, changing interpretation in genomic medicine, and practical concerns of returning results over time. Parent and adolescent groups focused on patient choice and personal utility of sequencing results. Each group expressed different views on the role of the child in decision-making and return of results. These discrepancies represent potential barriers to informed consent and a challenge for genetic counselors regarding the involvement of pediatric patients in decision-making and return of results discussions.

Relationship of youth involvement in diabetes-related decisions to treatment adherence.

The aim of this study was to examine the relationship of youth's involvement in diabetes-related decisions to adherence. Children and adolescents (8-19 years) and their parents (N = 89) completed the Decision Making Involvement Scale and the Self Care Inventory, a self-report measure of adherence. After controlling for youth age, the degree to which youth expressed an opinion and information to parents was associated with better parent- and youth-reported adherence. The degree to which parents expressed an opinion and information to youth was associated with worse parent-reported adherence. Joint decision-making behaviors (e.g., negotiation; provision of options) also were associated with better youth-reported adherence. Encouraging youth to express opinions and share illness-related information with parents during illness management discussions may improve adherence. Additional research is needed to identify mechanisms of effect and determine associations between decision making involvement and health behaviors and outcomes over time.