Identifying Opportunities and Challenges for Patients With Sarcoma as a Result of Comprehensive Genomic Profiling of Sarcoma Specimens.

PURPOSE: Comprehensive genomic profiling (CGP) of sarcomas is rapidly being integrated into routine clinical care to help refine diagnosis and prognosis and determine treatment. However, little is known about barriers to successful CGP or its clinical utility in sarcoma. We set out to determine whether CGP alters physician treatment decision-making, and whether sarcoma subtypes influence the frequency of successful technical performance of CGP. METHODS: A single-institution study evaluated profiling outcomes of 392 samples from patients with sarcoma, using a commercially available CGP panel. Of this group, 34 patients were evaluated prospectively (Decision Impact Trial) to evaluate the utility of CGP in physician decision-making. All cases were retrospectively analyzed to identify causes of CGP failure. RESULTS: CGP successfully interrogated 75.3% (n = 295 of 392) of patients with sarcoma. Bone sarcomas had lower passing rates at 65.3% (n = 32 of 49) compared with soft tissue sarcomas at 76.7% (n = 263 of 343; P = .0008). Biopsy location also correlated with profiling efficiency. Bone biopsy specimens had a 52.8% (n = 19 of 36) passing rate versus lung (61.1%; n = 33 of 54) and abdomen (80.1%; n = 109 of 136) specimens. CGP altered physician treatment selection in 25% of evaluable patients (n = 7 of 28) and was associated with improved progression-free survival. CONCLUSION: To our knowledge, this is the largest technical evaluation of the performance of CGP in sarcoma. CGP was effectively performed in the vast majority of sarcoma samples and altered physician treatment selection. Tumor location and tissue subtype were key determinants of profiling success and associated with preanalytic variables that affect DNA and RNA quality. These results support standardized biopsy collection protocols to improve profiling outcomes.

Does Previous Cardiac Surgery Predict Impaired Quality of Life in Adults With Congenital Heart Disease?

BACKGROUND: Improved survival of children with congenital heart disease (CHD) into adult life has led to further study of their quality of life (QoL) and its determinants. The QoL including the symptoms of anxiety and depression of adults with CHD was analyzed to determine the relationship, if any, between prior cardiac surgery and QoL. METHODS: Adults with CHD who were recruited from a single community-based cardiology practice completed self-reported questionnaires on their QoL, which included symptoms of anxiety and depression. Standard linear regression analysis was used to determine whether prior cardiac surgery predicted lower QoL scores. RESULTS: One hundred forty-nine adult patients with CHD were sent QoL questionnaires. Completed questionnaires were received from 135 patients: 71 (53%) males and 64 (47%) females, with a mean age of 26.3 years (standard deviation: 7.8, min: 17, max: 49). Respondents were assigned to two groups: those who had (n = 89, 66%) or had not (n = 46, 34%) previously undergone one or more cardiac surgical interventions. Results from standard linear regression analyses revealed no predictive relationship between history of previous cardiac surgery, whether one or more operations, and QoL. CONCLUSIONS: Among adult patients with CHD who completed QoL questionnaires, we observed no association between a patient's history of prior cardiac surgery and self-reported QoL measures. This welcome and important finding may be a reflection of the good functional capacity of both groups (postsurgical and nonsurgical) irrespective of the original CHD diagnosis and need for surgical intervention.

Postnatal Microstructural Developmental Trajectory of Corpus Callosum Subregions and Relationship to Clinical Factors in Very Preterm Infants.

Our objectives were to define the microstructural developmental trajectory of six corpus callosum subregions and identify perinatal clinical factors that influence early development of these subregions in very preterm infants. We performed a longitudinal cohort study of very preterm infants (32 weeks gestational age or younger) (N = 36) who underwent structural MRI and diffusion tensor imaging serially at four time points - before 32, 32, 38, and 52 weeks postmenstrual age. We divided the corpus callosum into six subregions, performed probabilistic tractography, and used linear mixed effects models to evaluate the influence of antecedent clinical factors on its microstructural growth trajectory. The genu and splenium demonstrated the most rapid developmental maturation, exhibited by a steep increase in fractional anisotropy. We identified several factors that favored greater corpus callosum microstructural development, including advancing postmenstrual age, higher birth weight, and college level or higher maternal education. Bronchopulmonary dysplasia, low 5-minute Apgar scores, caffeine therapy/apnea of prematurity and male sex were associated with reduced corpus callosum microstructural integrity/development over the first six months after very preterm birth. We identified a unique postnatal microstructural growth trajectory and associated clinical factor profile for each of the six corpus callosum subregions that is consistent with the heterogeneous functional role of these white matter subregions.

The relative predictive value of undergraduate versus graduate selection tools in two Australian medical schools.

Context: Monash University and the University of Western Australia admit both school-leavers and graduates into their Bachelor of Medicine and Bachelor of Surgery (MBBS) courses. The Undergraduate Medicine and Health Sciences Admission Test (UMAT) and the Graduate Medical Schools Admissions Test (GAMSAT) are used for selection, along with an academic score and an interview score. The aim of this study was to compare the relative predictive validity of the selected components in the two entry streams, particularly UMAT versus GAMSAT. Methods: Aggregated scores for course outcomes were calculated in the categories of knowledge, clinical and total scores, at four-time points. A path analysis was conducted based on multivariate regressions with model constraint parameters defined across the outcome variables to investigate change over time. Results: Academic scores were the strongest predictors of knowledge scores and end of course results. Interview scores had a small positive increasing effect, being stronger for clinical than knowledge outcomes. The effect size for GAMSAT was greater than for UMAT. Conclusions: Aptitude tests and interview scores added small but significant incremental predictive value to previous academic achievement. GAMSAT showed larger predictive value on outcomes than UMAT, for which one section (UMAT 3) had a negative effect.

Caregiver coping, mental health and child problem behaviours in cystic fibrosis: a cross-sectional study.

BACKGROUND: In children with cystic fibrosis (CF) sleep, eating/mealtime, physiotherapy adherence and internalising problems are common. Caregivers also often report elevated depression, anxiety and stress symptoms. PURPOSE: To identify, through principal components analysis (PCA), coping strategies used by Australian caregivers of children with CF and to assess the relationship between the derived coping components, caregiver mental health symptoms and child treatment related and non-treatment related problem behaviours. METHOD: One hundred and two caregivers of children aged 3 to 8 years from three CF clinic sites in Australia, completed self-report questionnaires about their coping and mental health and reported on their child's sleep, eating/mealtime, treatment adherence and internalising and externalising behaviours. RESULTS: Two caregiver coping components were derived from the PCA: labelled 'proactive' and 'avoidant' coping. 'Avoidant' coping correlated moderately with caregiver depression (0.52), anxiety (0.57) and stress (0.55). For each unit increase in caregiver use of avoidant coping strategies, the odds of frequent child eating/mealtime behaviour problems increased by 1.3 (adjusted 95 % CI 1.0 to 1.6, p = .03) as did the odds of children experiencing borderline/clinical internalising behaviour problems (adjusted 95 % CI 1.1 to 1.7, p = .01). Proactive coping strategies were not associated with reduced odds of any child problem behaviours. CONCLUSIONS: Avoidant coping strategies correlated with caregiver mental health and child problem behaviours. Intervening with caregiver coping may be a way to improve both caregiver mental health and child problem behaviours in pre-school and early school age children with CF.

The natural history and predictors of persistent problem behaviours in cystic fibrosis: a multicentre, prospective study.

BACKGROUND: In cystic fibrosis (CF), problems with sleep, eating/mealtime behaviours, physiotherapy adherence and parental mental health issues are common, yet their natural history and the extent of service use to address them are unknown. OBJECTIVE: Follow up the 2007 cohort to determine: (1) prevalence of child sleep, eating/mealtime behaviours, physiotherapy adherence, and externalising/internalising problem behaviours and primary caregiver mental health status after a 3-year period; (2) natural history of child behaviours; (3) potentially modifiable predictors of persistent problems; and (4) service use for behaviours. DESIGN: Prospective cohort. SETTING: Royal Children's Hospital, Monash Medical Centre and Sydney Children's Hospital (Australia) CF clinics. PARTICIPANTS: Caregivers, of children aged 3-8 years, who completed the baseline questionnaire. MAIN OUTCOME MEASURES: Child sleep, eating/mealtime behaviours, adherence with therapy and externalising and internalising behaviours. PREDICTORS: parenting style (low warmth), caregiver mental health status and sleep quality at baseline. RESULTS: 102 of 116 (88%) families participated. The prevalence of sleep and eating/mealtime problems at follow-up was similar to baseline. The prevalence of caregiver mental health symptoms remained higher than the community data. 71 out of 102 (70%) of the children experienced at least one persistent behaviour problem. Caregiver mental health difficulties predicted persistent child moderate to severe sleep problems (adjusted OR 6.5, 95% CI 1.2 to 36.2, p=0.03) and their persistently poor adherence to the physiotherapy regimen (adjusted OR 3.5, 95% CI 1.3 to 9.2, p=0.01). CONCLUSIONS: Child problem behaviours are common in children with CF, persist and are often predicted by the mental health of the parent. Routine surveillance for and management of child problem behaviours are recommended.