"Why We Keep Coming Back": Family and Provider Perspectives on Factors Influencing Long-term Follow-up for Pediatric Cancer Survivorship Care.

PURPOSE: The majority of childhood cancer survivors do not follow-up for long-term risk-based screening for recurrent illness and treatment late effects, despite a high prevalence of secondary morbidities. The primary aim of this study was to investigate factors that influence long-term follow-up for survivorship care, from the perspectives of providers, patients, and caregivers. MATERIALS AND METHODS: A semistructured interview was designed to elicit stakeholder perspectives on factors that facilitate or impede routine clinic visits after completion of cancer therapy. Results were analyzed using a qualitative framework method. RESULTS: Providers, patients, and caregivers identified a wide range of factors that might influence long-term follow-up for care. All respondents noted the importance of efficient clinical operations, resources such as parking, provider behaviors, rapport/attachment, and patient/family logistics. Compared with patients/caregivers, providers more frequently mentioned institutional operations, their own education and skills, patient/family understanding and motivation, and interpersonal processes such as communication style. Families more frequently mentioned clinic environment, and patients more frequently noted the importance of having a family member present, something neither providers nor caregivers reported. CONCLUSIONS: Providers, patients, and patient caregivers have different perspectives regarding factors that may influence follow-up for long-term survivorship care. Understanding these differences can help inform efforts to improve follow-up.

Costello syndrome: Clinical phenotype, genotype, and management guidelines.

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence-based guidelines due to the lack of data for this rare condition.

Neurocognitive and executive functioning in adult survivors of congenital heart disease.

OBJECTIVE: Congenital heart disease (CHD) can affect the developing central nervous system, resulting in neurocognitive and behavioral deficits. Preoperative neurological abnormalities as well as sequelae of the open heart operations required to correct structural abnormalities of the heart contribute to these deficits. There are few studies examining the neurocognitive functioning of adults with CHD. This study sought to investigate multiple domains of neurocognitive functioning in adult survivors of CHD who had childhood cardiac surgery with either moderate or severe disease complexity. DESIGN: A total of 48 adults (18-49 years of age) who had undergone cardiac surgery for CHD prior to five years of age participated in the study. CHD severity was classified as moderate or severe according to the 32nd Bethesda Guidelines. A computerized battery of standardized neurocognitive tests (CNS-Vital Signs), a validated rating scale of executive functioning, and demographic questionnaires were administered. RESULTS: There were no significant differences between the moderate CHD group and normative data on any cognitive measure. In contrast, the severe CHD group differed from norms in multiple domains: psychomotor speed, processing speed, complex attention, reaction time, and on the overall neurocognitive index. Number of surgeries was strongly related to worse executive functioning. There was no association between age at first surgery or time since last surgery and neuropsychological functioning. Number of surgeries was also unrelated to neurocognitive test performance. CONCLUSIONS: Patients with severe CHD performed significantly worse on measures of processing speed, attention, and executive functioning. These findings may be useful in the long-term care of adults with congenital heart disease.

Predictors of Suboptimal Follow-up in Pediatric Cancer Survivors.

Attendance to follow-up care after completion of cancer treatment is an understudied area. We examined demographic, clinical, and socioeconomic predictors of follow-up by pediatric cancer patients at a large center in 442 newly diagnosed patients using multivariable logistic regression analyses. Patients who did not return to clinic for at least 1000 days were considered lost to follow-up. Two hundred forty-two (54.8%) patients were lost. In multivariable analyses, the following variables were independent predictors of being lost to follow-up: treatment with surgery alone (odds ratio [OR]=6.7; 95% confidence interval [CI], 3.1-14.9), older age at diagnosis (reference, 0 to 4; ages, 5 to 9: OR=1.8, 95% CI, 1.1-3; ages, 10 to 14: OR=3.3; CI, 1.8-6.1; and ages, 15 and above: OR=4.8; CI, 2.1-11.7), lack of history of stem cell transplantation (OR=2, 95% CI, 1.04-3.7) and lack of insurance (OR=3.4; CI, 1.2-9.2). Hispanic patients had the best follow-up rates (53.7%) compared to whites and blacks (P=0.03). Attendance to long-term follow-up care is suboptimal in childhood cancer survivors. Predictors that were associated with nonattendance can be used to design targeted interventions to improve follow-up care for survivors of pediatric cancer.

Verbal memory functioning in adolescents and young adults with Costello syndrome: evidence for relative preservation in recognition memory.

Costello syndrome (CS) is a rare genetic disorder caused by germline mutations in the HRAS proto-oncogene which belongs to the family of syndromes called rasopathies. HRAS plays a key role in synaptic long-term potentiation (LTP) and memory formation. Prior research has found impaired recall memory in CS despite enhancement in LTP that would predict memory preservation. Based on findings in other rasopathies, we hypothesized that the memory deficit in CS would be specific to recall, and that recognition memory would show relative preservation. Memory was tested using word-list learning and story memory tasks with both recall and recognition trials, a design that allowed us to examine these processes separately. Participants were 11 adolescents and young adults with molecularly confirmed CS, all of whom fell in the mild to moderate range of intellectual disability. Results indicated a clear dissociation between verbal recall, which was impaired (M = 69 ± 14), and recognition memory, which was relatively intact (M = 86 ± 14). Story recognition was highly correlated with listening comprehension (r = 0.986), which also fell in the low-average range (M = 80 ± 12.9). Performance on other measures of linguistic ability and academic skills was impaired. The findings suggest relatively preserved recognition memory that also provides some support for verbal comprehension. This is the first report of relatively normal performance in a cognitive domain in CS. Further research is needed to better understand the mechanisms by which altered RAS-MAPK signaling affects neuronal plasticity and memory processes in the brain.

Neurocognitive, adaptive, and behavioral functioning of individuals with Costello syndrome: a review.

Costello syndrome is a rare rasopathy resulting from germline mutations of the proto-oncogene HRAS. Its phenotype includes severe failure-to-thrive, cardiac abnormalities, a predisposition to benign and malignant tumors, hypotonia, and developmental delay. Costello syndrome is associated with cognitive impairment, including intellectual functioning generally in the mild to moderate range of disability, commensurate adaptive functioning, and increased anxiety. Relative strengths have been found for nonverbal fluid reasoning (FR). Gender effects have been reported, with females showing better adaptive functioning across domains. Developmentally, nonverbal skills plateau in late childhood/early adolescence, whereas the rate of vocabulary acquisition may increase in adolescence into early adulthood. Here we review the literature assessing cognitive, adaptive, and behavioral functioning in Costello syndrome, and we provide data from an ongoing longitudinal study. Severity of cognitive impairment may depend upon the specific HRAS mutation, as three individuals with the p.G13C change showed average nonverbal FR skills and borderline-to-low average overall nonverbal IQ. Further, separation anxiety is more common in Costello syndrome than in the general population, affecting 39% of this cohort, and males are more often overly anxious than females. Interrelations between anxiety and cognitive and adaptive functioning were found, pointing to functional difficulties as a likely source of stress and anxiety. Taking into account data from animal models, cognitive and behavioral changes likely originate from abnormal differentiation of neuronal precursor cells, which result in structural and functional brain differences.

Feasibility, acceptability, and predictive validity of a psychosocial screening program for children and youth newly diagnosed with type 1 diabetes.

OBJECTIVE: Psychosocial screening has been recommended for pediatric patients with newly diagnosed type 1 diabetes and their families. Our objective was to assess a psychosocial screening protocol in its feasibility, acceptability to families, and ability to predict early emerging complications, nonadherent family behavior, and use of preventive psychology services. RESEARCH DESIGN AND METHODS: A total of 125 patients and their caregivers were asked to participate in a standardized screening interview after admission at a large urban children's hospital with a new diagnosis of type 1 diabetes. Medical records were reviewed for subsequent diabetes-related emergency department (ED) admissions, missed diabetes clinic appointments, and psychology follow-up within 9 months of diagnosis. RESULTS: Of 125 families, 121 (96.8%) agreed to participate in the screening, and a subsample of 30 surveyed caregivers indicated high levels of satisfaction. Risk factors at diagnosis predicted subsequent ED admissions with a sensitivity of 100% and a specificity of 98.6%. Children from single-parent households with a history of behavior problems were nearly six times more likely to be seen in the ED after diagnosis. Missed appointments were likeliest among African Americans, 65% of whom missed at least one diabetes-related appointment. Psychology services for preventive intervention were underutilized, despite the high acceptability of the psychosocial screening. CONCLUSIONS: Psychosocial screening of newly diagnosed patients with type 1 diabetes is feasible, acceptable to families, and able to identify families at risk for early emerging complications and nonadherence. Challenges remain with regards to reimbursement and fostering follow-up for preventive care.

Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome.

Costello syndrome is a rare rasopathy caused by germline mutations in the oncogene HRAS resulting in increased signal transduction through the Ras/mitogen-activated protein kinase pathway. In contrast to the more common rasopathies, such as neurofibromatosis type 1 and Noonan syndrome, limited information is available on standardized cognitive testing in this cohort. Past research indicated a mean average IQ in the mild mental retardation range, with strengths in fluid reasoning (FR) and weakness in expressive language, as well as static skills over time. Here we report on standardized IQ and adaptive functioning in 18 individuals with Costello syndrome, nine males and nine females, and longitudinal development for 11 who had previous testing. The overall IQ, ranging from severe mental retardation to the average range, with a mean in the mildly mentally retarded range, was again found to be stable, but an interesting pattern in the development of nonverbal FR was identified. Participants showed an improvement in nonverbal FR, followed by stable skills thereafter, suggesting a "late bloomer" effect in late childhood/early adolescence. Overall adaptive functioning fell into the range of Intellectual Disability for 70% of subjects, with Socialization as a relative strength and Daily Living Skills an area of relative difficulty. Interestingly, females were found to be higher functioning than males in all domains, including Communication, Daily Living Skills and Socialization. Caregivers reported significantly more behavioral concerns in males, including internalizing, externalizing, and other maladaptive behaviors. In contrast, no gender differences were found in cognitive or visuomotor functioning.

Comparison of single-level cervical fusion and a metal-on-metal cervical disc replacement device.

Cervical fusion is the common treatment for cervical disc disease but can cause secondary disorders. The Prestige ST cervical disc prosthesis (Medtronic Sofamor Danek, Memphis, TN) was designed to preserve spinal motion to potentially limit the secondary disorders. In this article, we report 2-year results from a single-center study comparing use of this device with use of anterior cervical discectomy and fusion (ACDF). Nineteen patients were prospectively randomized to receive the device or to undergo ACDF. Twenty-four months after surgery, patients who received the device demonstrated improvement in neck pain, arm pain, and neurologic function. In our cohort, patients who underwent arthroplasty demonstrated greater improvement in neurologic function and neck pain than patients who underwent cervical discectomy and fusion.