Staged Versus Complete Repair in the Symptomatic Neonate With Tetralogy of Fallot.

BACKGROUND: The optimal management of tetralogy of Fallot (TOF) in symptomatic neonates remains unknown. We compared outcomes for those undergoing palliation vs complete repair in the neonatal period. METHODS: In a retrospective cohort study of symptomatic neonates with TOF who had a neonatal complete repair (group 1, n = 112) or staged repair (group 2, n = 26) from 2000 to 2013, we compared outcomes at 4 time points: neonatal complete repair vs palliation (group 1 vs 2A), neonatal vs later complete repair (group 1 vs 2B), the single vs combined admissions to achieve a complete repair (group 1 vs group 2A + 2B), and cumulative events 2 years after complete repair for both groups. RESULTS: Demographics, anatomy, comorbidities, surgical approach, and mortality were similar between groups 1 and 2. Group 1 had a longer duration of cardiopulmonary bypass and deep hypothermic circulatory arrest and more postprocedure cardiac events compared with group 2A; a longer duration of intubation, intensive care, and postprocedure hospital stay compared with groups 2A and 2B; and a longer total hospital stay compared with group 2B. With combined admissions for group 2, there was no difference in the total duration of intensive care, total hospital stay, or reinterventions compared with group 1. CONCLUSIONS: Both management options result in similar survival; however, early morbidity was greater with neonatal complete repair. The impact of increased neonatal exposures, such as cardiopulmonary bypass, deep hypothermic circulatory arrest, and intensive care, on neurocognitive development requires further study but should be considered when choosing an optimal strategy.

Red cell transfusion practices after stage 1 palliation: a survey of practitioners from the Pediatric Cardiac Intensive Care Society.

INTRODUCTION: Neonates may require increased red cell mass to optimise oxygen content after stage 1 palliation; however, data informing transfusion practices are limited. We hypothesise there is a patient-, provider-, and institution-based heterogeneity in red cell transfusion decision-making after stage 1 palliation. METHODS: We conducted an online survey of Pediatric Cardiac Intensive Care Society practitioners in 2016. Respondents answered scenario-based questions that defined transfusion indications and identified haematocrit transfusion thresholds. Respondents were divided into restrictive and liberal groups based on a haematocrit score. Fisher's exact test was used to determine the associations between transfusion likelihood and patient, provider, and institutional characteristics. Bonferroni correction was applied to adjust the p-value to 0.004 for multiple comparisons. RESULTS: There was a 21% response rate (116 responses). Most were male (58.6%), attending physicians (85.3%) with >5 year of intensive care experience (88.7%) and subspeciality training in critical care medicine (47.4%). The majority of institutions were academic (96.6%), with a separate cardiac ICU (86.2%), and performed >10 stage 1 palliation cases annually (68.1%). After Bonferroni correction, there were no significant patient, respondent, or institutional differences between the restrictive and liberal groups. No respondent or institutional characteristics influenced transfusion decision-making after stage 1 palliation. CONCLUSIONS: Decision-making around red cell transfusion after stage 1 palliation is heterogeneous. We found no clear relationships between patient, respondent, or institutional characteristics and transfusion decision-making among surveyed respondents. Given the lack of existing data informing red cell transfusion after stage 1 palliation, further studies are necessary to inform evidence-based guidelines.

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials.

PURPOSE: To report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector-based gene therapy for RPE65 mutation-associated inherited retinal dystrophy (IRD), including results of a phase 1 follow-on study at year 4 and phase 3 study at year 2. DESIGN: Open-label phase 1 follow-on clinical trial and open-label, randomized, controlled phase 3 clinical trial. PARTICIPANTS: Forty subjects who received 1.5×1011 vector genomes (vg) of VN per eye in at least 1 eye during the trials, including 11 phase 1 follow-on subjects and 29 phase 3 subjects (20 original intervention [OI] and 9 control/intervention [CI]). METHODS: Subretinal injection of VN in the second eye of phase 1 follow-on subjects and in both eyes of phase 3 subjects. MAIN OUTCOME MEASURES: End points common to the phase 1 and phase 3 studies included change in performance on the Multi-Luminance Mobility Test (MLMT) within the illuminance range evaluated, full-field light sensitivity threshold (FST) testing, and best-corrected visual acuity (BCVA). Safety end points included adverse event reporting, ophthalmic examination, physical examination, and laboratory testing. RESULTS: Mean (standard deviation) MLMT lux score change was 2.4 (1.3) at 4 years compared with 2.6 (1.6) at 1 year after administration in phase 1 follow-on subjects (n = 8), 1.9 (1.1) at 2 years, and 1.9 (1.0) at 1 year post-administration in OI subjects (n = 20), and 2.1 (1.6) at 1 year post-administration in CI subjects (n = 9). All 3 groups maintained an average improvement in FST, reflecting more than a 2 log10(cd.s/m2) improvement in light sensitivity at 1 year and subsequent available follow-up visits. The safety profile was consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred. CONCLUSIONS: After VN gene augmentation therapy, there was a favorable benefit-to-risk profile with similar improvement demonstrated in navigational ability and light sensitivity among 3 groups of subjects with RPE65 mutation-associated IRD, a degenerative disease that progresses to complete blindness. The safety profile is consistent with the administration procedure. These data suggest that this effect, which is nearly maximal by 30 days after VN administration, is durable for 4 years, with observation ongoing.

Development of the Serum α-Fetoprotein Reference Range in Patients with Beckwith-Wiedemann Spectrum.

OBJECTIVE: To establish reference ranges for serum α-fetoprotein (AFP) at various ages in patients with Beckwith-Wiedemann spectrum (BWSp), to better predict the risk for hepatoblastoma in this population. STUDY DESIGN: A retrospective analysis of AFP measurements collected from patients with BWSp was performed. Factors including sex, prematurity, molecular diagnosis of patients, and performing laboratory were evaluated for significant differences. In total, 1372 AFP values were collected from 147 patients and the predictive AFP values at various ages were calculated to establish reference ranges. Mixed-effects polynomial regression models were used to study various potential factors affecting log(AFP) values. RESULTS: Overall, predicted AFP values declined to normal range for age (<10 ng/mL) by 14 months old. Patient sex and performing laboratory were found not to influence values. A significant difference was demonstrated between premature and nonpremature patients, and separate reference values were established. Significant differences in the predicted AFP value were not broadly apparent between molecular subtypes; however, interpretation was limited due to the small sample size of some of these subtypes. CONCLUSIONS: Predictive AFP values were created for premature and nonpremature patients with BWSp to aid with interpretation and monitoring of the risk for hepatoblastoma. Further analysis is needed to determine whether AFP values differ within the less common molecular subtypes of patients with BWSsp.

Enrollee Characteristics in an Intensive Tobacco Dependence Treatment Program: The Relationship of Race and Sex to Demographic Factors and Tobacco Use Patterns.

Intensive tobacco treatment programs offer many advantages relative to other treatment options, particularly for more complex patients, e.g., highly nicotine dependent, or those with medical and psychiatric symptoms and disorders. Efforts to better understand those who choose to enroll in these programs, particularly regarding the characteristics they possess known to mediate outcomes, are important considerations in tailoring available services. In this study, we examined how participants differed on key descriptive and tobacco use variables within race (i.e., African-American, Caucasian) and sex subgroups. Baseline characteristics from a large group of consecutive program enrollees were examined across targeted subgroups. Strong racial effects and some sex effects were noted for marital status, education, employment and health insurance status, alcohol consumption, presence of medical and psychiatric disorders, as well as participant tobacco use patterns and tobacco use rates of family, friends and coworkers. The differences in participant tobacco use measures across race and sex factors remained significant after adjusting for the confounding effects of all other covariates. These findings have implications for characterizing key patient subgroups who present at tobacco treatment clinics. Such information may contribute to options for tailoring treatment regimens.

Use of Intravenous Acetaminophen in Children for Analgesia After Spinal Fusion Surgery: A Randomized Clinical Trial.

OBJECTIVES: Opioid pharmacotherapy is the cornerstone of postoperative analgesia. Despite its effectiveness, it has a variety of potential adverse effects. Therefore, a multimodal approach with non-opioid analgesics would be optimal. The aim of this study was to determine if intravenous (IV) acetaminophen would reduce opioid requirements and improve clinical outcomes in children after surgery. METHODS: A single-center, randomized, double-blind study was conducted in 57 children (10-18 years old) undergoing posterior spine fusion surgery between July 2011 to May 2014. All subjects received either acetaminophen or placebo at the end of surgery, followed by repeated doses every 6 hours for a total of 8 doses. RESULTS: In the first 24 postoperative hours, the average opioid consumption was lower for the active group compared with the placebo group (p = 0.02). The total unadjusted time to patient controlled analgesia (PCA) discontinuation was also longer in the placebo group than the active group (90 hours vs. 73 hours, p = 0.02); however, this was not statistically significant after normalizing for body weight. Additionally, time to first solid intake was longer without the use of acetaminophen (69 hours vs. 49 hours, p = 0.01). CONCLUSIONS: Postoperative use of IV acetaminophen was associated with earlier time to diet advancement and discontinuation of IV analgesics and may result in lower opioid consumption.

Predictors of Length of Hospital Stay After Complete Repair for Tetralogy of Fallot: A Prospective Cohort Study.

BACKGROUND: We sought to identify patient and surgical factors associated with time to hospital discharge in patients undergoing complete repair for tetralogy of Fallot. METHODS AND RESULTS: We performed a prospective cohort study of patients with tetralogy of Fallot admitted for complete repair between May 1, 2012 and June 2, 2017 at Children's Hospital of Philadelphia with detailed demographic, clinical, and operative characteristics. The primary outcome was time to hospital discharge. Cox proportional hazards models were used to identify patient and operative predictors of time to hospital discharge. We enrolled 151 subjects, 62.8% male, 65.6% non-Hispanic white, and 9.9% non-Hispanic black. The median time to hospital discharge was 7 days (interquartile range 4, 12). Five patients died in the hospital, all of whom underwent tetralogy of Fallot repair beyond the neonatal period. Greater birth weight was associated with higher rate of hospital discharge (hazard ratio [HR]=1.35, 95% confidence interval (CI) =1.11, 1.64), while absent pulmonary valve versus pulmonary stenosis (HR=0.27, 95% CI=0.08, 0.91), pulmonary valve atresia versus pulmonary stenosis (HR=0.57, 95% CI=0.33, 0.97), presence of aortopulmonary collaterals (HR=0.44, 95% CI=0.24, 0.84), complete repair performed in the neonatal period (<30 days of life) (HR=0.45, 95% CI=0.27, 0.75), more than 1 cardiopulmonary bypass run (HR=0.33, 95% CI=0.18, 0.61), and longer aortic cross-clamp time (HR [per 10 minutes]=0.88, 95% CI=0.79, 0.97) were associated with lower rate of hospital discharge. CONCLUSIONS: Postoperative hospital stay after complete repair of tetralogy of Fallot is in part determined by patient and operative factors. Some (eg, surgical strategy for the symptomatic neonate) may be modifiable. These results may impact patient counseling, choice of surgical approach, and postoperative care.

Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Phase 1 studies have shown potential benefit of gene replacement in RPE65-mediated inherited retinal dystrophy. This phase 3 study assessed the efficacy and safety of voretigene neparvovec in participants whose inherited retinal dystrophy would otherwise progress to complete blindness. METHODS: In this open-label, randomised, controlled phase 3 trial done at two sites in the USA, individuals aged 3 years or older with, in each eye, best corrected visual acuity of 20/60 or worse, or visual field less than 20 degrees in any meridian, or both, with confirmed genetic diagnosis of biallelic RPE65 mutations, sufficient viable retina, and ability to perform standardised multi-luminance mobility testing (MLMT) within the luminance range evaluated, were eligible. Participants were randomly assigned (2:1) to intervention or control using a permuted block design, stratified by age (<10 years and ≥10 years) and baseline mobility testing passing level (pass at ≥125 lux vs <125 lux). Graders assessing primary outcome were masked to treatment group. Intervention was bilateral, subretinal injection of 1·5 × 1011 vector genomes of voretigene neparvovec in 0·3 mL total volume. The primary efficacy endpoint was 1-year change in MLMT performance, measuring functional vision at specified light levels. The intention-to-treat (ITT) and modified ITT populations were included in primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00999609, and enrolment is complete. FINDINGS: Between Nov 15, 2012, and Nov 21, 2013, 31 individuals were enrolled and randomly assigned to intervention (n=21) or control (n=10). One participant from each group withdrew after consent, before intervention, leaving an mITT population of 20 intervention and nine control participants. At 1 year, mean bilateral MLMT change score was 1·8 (SD 1·1) light levels in the intervention group versus 0·2 (1·0) in the control group (difference of 1·6, 95% CI 0·72-2·41, p=0·0013). 13 (65%) of 20 intervention participants, but no control participants, passed MLMT at the lowest luminance level tested (1 lux), demonstrating maximum possible improvement. No product-related serious adverse events or deleterious immune responses occurred. Two intervention participants, one with a pre-existing complex seizure disorder and another who experienced oral surgery complications, had serious adverse events unrelated to study participation. Most ocular events were mild in severity. INTERPRETATION: Voretigene neparvovec gene replacement improved functional vision in RPE65-mediated inherited retinal dystrophy previously medically untreatable. FUNDING: Spark Therapeutics.

Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial.

BACKGROUND: Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study. METHODS: In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5 × 10(11) vector genomes) in a total volume of 300 µL was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389. FINDINGS: No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline). INTERPRETATION: To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease. FUNDING: Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Genetic Risk Scores Implicated in Adult Bone Fragility Associate With Pediatric Bone Density.

Using adult identified bone mineral density (BMD) loci, we calculated genetic risk scores (GRS) to determine if they were associated with changes in BMD during childhood. Longitudinal data from the Bone Mineral Density in Childhood Study were analyzed (N = 798, 54% female, all European ancestry). Participants had up to 6 annual dual energy X-ray scans, from which areal BMD (aBMD) Z-scores for the spine, total hip, and femoral neck were estimated, as well as total body less head bone mineral content (TBLH-BMC) Z-scores. Sixty-three single-nucleotide polymorphisms (SNPs) were genotyped, and the percentage of BMD-lowering alleles carried was calculated (overall adult GRS). Subtype GRS that include SNPs associated with fracture risk, pediatric BMD, WNT signaling, RANK-RANKL-OPG, and mesenchymal stem cell differentiation were also calculated. Linear mixed effects models were used to test associations between each GRS and bone Z-scores, and if any association differed by sex and/or chronological age. The overall adult, fracture, and WNT signaling GRS were associated with lower Z-scores (eg, spine aBMD Z-score: ßadult = -0.04, p = 3.4 × 10(-7) ; ßfracture = -0.02, p = 8.9 × 10(-6) ; ßWNT = -0.01, p = 3.9 × 10(-4) ). The overall adult GRS was more strongly associated with lower Z-scores in females (p-interaction ≤ 0.05 for all sites). The fracture GRS was more strongly associated with lower Z-scores with increasing age (p-interaction ≤ 0.05 for all sites). The WNT GRS associations remained consistent for both sexes and all ages (p-interaction > 0.05 for all sites). The RANK-RANKL-OPG GRS was more strongly associated in females with increasing age (p-interaction < 0.05 for all sites). The mesenchymal stem cell GRS was associated with lower total hip and femoral neck Z-scores, in both boys and girls, across all ages. No associations were observed between the pediatric GRS and bone Z-scores. In conclusion, adult identified BMD loci associated with BMD and BMC in the pediatric setting, especially in females and in loci involved in fracture risk and WNT signaling.

Intraoperative dexmedetomidine reduces postoperative mechanical ventilation in infants after open heart surgery.

OBJECTIVE: The inclusion of dexmedetomidine in the operative and postoperative management of infants with congenital heart defects has lessened the need for opioids that may cause respiratory depression. Our objective was to show that a dexmedetomidine bolus at or about the time of sternal closure is associated with a decrease in the use of mechanical ventilation in the immediate postoperative period. DESIGN: Retrospective cohort study. SETTING: Single pediatric tertiary cardiac center. PATIENTS: Infants undergoing surgical intervention for congenital heart defects requiring cardiopulmonary bypass, age 30-365 days in a 5-year time period from June 1, 2008, to December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,057 total encounters, 441 met inclusion criteria and were evenly distributed over the 5-year time period. Dexmedetomidine had been given at or about the time of sternal closure in 57% of patients. When the exposed and unexposed groups were compared in terms of mechanical ventilation immediately postoperative, there was a statistically significant effect of using dexmedetomidine on the odds of receiving mechanical ventilation (p = 0.0019). This difference remained significant after adjusting for covariates affecting the decision for mechanical ventilation, including year of the procedure, age and weight of subject, cardiopulmonary bypass time, the use of deep hypothermic circulatory arrest, intraoperative fentanyl dose, and the Risk Adjustment for Congenital Heart Surgery Score 1 (p = 0.0317). The odds of receiving mechanical ventilation are estimated to be two times higher for patients who did not receive dexmedetomidine than for patients who received dexmedetomidine after adjusting for variables. CONCLUSION: The use of dexmedetomidine bolus in the operating room at the time of sternal closure in infants undergoing open heart surgery is associated with reduced need for mechanical ventilation in the immediate postoperative period.

Tobacco dependence treatment: influence of training experiences on clinical activities among otolaryngologists.

OBJECTIVES/HYPOTHESIS: Although one in five U.S. adults continue to smoke, healthcare providers often fail to provide basic, effective interventions. This is particularly true for physician specialists. This study sought to investigate perceived role, self-efficacy, practice behaviors, and attitudes among otolaryngologists as they relate to the delivery of tobacco treatment services. STUDY DESIGN: This study involved a single administration of a survey questionnaire to current members of the American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS). METHODS: A questionnaire was mailed up to three times to active members. RESULTS: Survey response rate was 39% (N = 2127). Based on an evaluation of treatment factors categorized according to the National Cancer Institute's 5A's approach, trained providers generally rated themselves consistently higher than untrained providers across areas of clinical activity. Minimal differences were noted for Ask and Advise, moderate for Assess, and the greatest for Assist and Arrange. Trained providers also indicated more positive attitudes towards treatment. CONCLUSIONS: While the level of performance was reasonable for otolaryngologists relative to other specialists in the published literature, overall tobacco treatment activity remains unacceptably low. This study suggests the positive impact of training and the potential value of making such experiences widely available.

Locally advanced squamous cell carcinoma of the head and neck: CT texture and histogram analysis allow independent prediction of overall survival in patients treated with induction chemotherapy.

PURPOSE: To determine if computed tomographic (CT) texture and histogram analysis measurements of the primary mass are independently associated with overall survival in patients with locally advanced squamous cell carcinoma of the head and neck who were previously treated with cisplatin, 5-fluorouracil, and docetaxel (TPF) induction chemotherapy. MATERIALS AND METHODS: This institutional review board-approved retrospective study included 72 patients with locally advanced squamous cell carcinoma of the head and neck who were treated with induction TPF chemotherapy in 2004-2010. CT texture and histogram analysis of the primary mass on the pretherapy CT images were performed by using TexRAD software before and after application of spatial filters at different anatomic scales ranging from fine detail to coarse features. Cox proportional hazards models were used to examine the association between overall survival and the baseline CT imaging measurements and clinical variables. RESULTS: Primary mass entropy and skewness measurements with multiple spatial filters were associated with overall survival. Multivariate Cox regression analysis incorporating clinical and imaging variables indicated that primary mass size (hazard ratio [HR], 1.58 for each 1-cm increase; P = .018), N stage (HR, 8.77 for N3 vs N0 or N1; P = .002; HR, 4.99 for N3 vs N2; P = .001), and primary mass entropy (HR, 2.10 for each 0.5-unit increase; P = .036) and skewness (HR, 3.67 for each 1.0-unit increase; P = .009) measurements with the 1.0 spatial filter were independently associated with overall survival. CONCLUSION: Independent of tumor size, N stage, and other clinical variables, primary mass CT texture and histogram analysis parameters are associated with overall survival in patients with locally advanced squamous cell carcinoma of the head and neck who were treated with induction TPF. Online supplemental material is available for this article.

Self-monitoring as a mediator of weight loss in the SMART randomized clinical trial.

BACKGROUND: Integral components of behavioral weight-loss treatment include self-monitoring of diet and physical activity along with feedback to participants regarding their behaviors. While providing feedback has been associated with weight loss, no studies have examined the impact of feedback frequency on weight loss or the mediating role of self-monitoring adherence in this relationship. PURPOSE: This study examined the effect of participant feedback frequency on weight loss and determined if this effect was mediated by adherence to self-monitoring in a behavioral weight-loss trial conducted in the USA. METHOD: Participants (N = 210) were randomly assigned to one of three self-monitoring methods with either no-daily feedback messages or daily feedback messages: (1) paper diary (PD), no-daily feedback; (2) personal digital assistant (PDA), no-daily feedback; and (3) PDA, daily tailored feedback messages (PDA + FB). The Sobel test via bootstrapping examined the direct effect of feedback frequency on weight loss and the indirect effect through self-monitoring adherence. RESULTS: Receiving daily feedback messages significantly increased participants' self-monitoring adherence. A significant effect of feedback frequency on weight loss was noted; however, after adjusting for self-monitoring adherence, the effect of feedback frequency on weight loss was no longer significant. Feedback frequency had a significant indirect effect on weight loss through self-monitoring adherence. CONCLUSION: Self-monitoring adherence mediated the effect of feedback frequency on weight loss. Increasing the frequency with which participants receive feedback could enhance self-monitoring adherence, a critical component of behavioral weight-loss treatment.

Physical activity self-monitoring and weight loss: 6-month results of the SMART trial.

INTRODUCTION: Weight loss has been associated with higher physical activity (PA) levels and frequent dietary self-monitoring. Less is known about how PA self-monitoring affects adherence to PA goals, PA levels, and weight change. METHODS: The SMART Trial is a clinical weight loss trial in which 210 overweight adults were randomized equally to one of three arms: 1) paper record (PR), 2) personal digital assistant with self-monitoring software (PDA), and 3) PDA with daily tailored feedback message (PDA + FB). PA self-monitoring and adherence to PA goals were based on entries in weekly submitted diaries. PA levels were measured via self-report by the past 6-month Modifiable Activity Questionnaire at baseline and 6 months. RESULTS: Data are presented on 189 participants with complete 6-month PA data (84% female, 77% white, mean age = 47.3 ± 8.8 yr, mean body mass index = 34.1 ± 4.5 kg·m(-2)). Median PA level was 7.96 MET·h·wk(-1) at baseline and 13.4 MET·h·wk(-1) at 6 months, with significant PA increases in all three arms. PDA + FB arm had a higher mean number of weekly self-monitoring entries than the PR arm (3.4 vs 2.4, P = 0.003) and were more likely to maintain high (i.e., 100%) adherence to PA goals over time than the PDA (P = 0.02) or PR arms (P = 0.0003). Both PA self-monitoring and adherence to PA goals were related to higher PA levels at 6 months. A higher mean rate of PA self-monitoring was associated with a greater percentage of weight decrease (ρ = -0.49, P < 0.0001) at 6 months. CONCLUSIONS: PA self-monitoring and adherence to PA goals were more likely in participants in the PDA + FB arm and in turn predicted higher PA levels and weight loss.