Psychosocial Assessment Rather Than Severity of Liver Failure Dominates Selection for Liver Transplantation in Patients With Alcohol-Related Liver Disease.

The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a validated interview tool to assess psychosocial well-being in candidates for solid organ transplants, with higher scores indicating greater vulnerability. We hypothesized that patients with alcohol-related liver disease (ALD) undergoing liver transplantation (LT) evaluation would have higher SIPAT scores than candidates with non-ALD, but that only patients with ALD who have low scores would be selected. We analyzed retrospectively consecutive adults undergoing LT evaluation from June 2018 to December 2019. Comparisons between patients with ALD and patients with non-ALD were made using the nonparametric Wilcoxon rank sum test plus a multivariate analysis to determine independent predictors for approval. In the study cohort of 358 patients, there were 199 (56%) patients with ALD with a mean age of 55 years, and 133 (67%) were men. There were 159 (44%) patients with non-ALD with a mean age of 57 years, and 95 (60%) were men. Mean Model for End-Stage Liver Disease-sodium scores were similar for selected versus not selected patients with ALD (25 versus 25.6) and selected versus not selected patients with non-ALD (18.3 versus 17.4), although the ALD group had substantially higher Model for End-Stage Liver Disease scores. Patients with ALD had higher mean SIPAT composite and individual domain scores compared with their non-ALD counterparts. SIPAT scores were not affected by age or sex. Proportionately more candidates with non-ALD were selected compared to candidates with ALD (68% versus 42%; P < 0.001; odds ratio for approval of non-ALD versus ALD, 2.9; 95% confidence interval, 1.8-4.7; P < 0.001). Composite SIPAT scores were lower in the selected versus nonselected in both ALD and non-ALD groups, although the SIPAT scores were significantly higher in selected patients with ALD (median, 39) than selected patients with non-ALD (median, 23; P = 0.001). Psychosocial assessment has a greater influence than acuity of liver failure on the selection of patients with ALD for LT listing, whereas psychosocial assessment has a minor influence on the selection of non-ALD candidates.

Depression, Anxiety, and Daily Activity Among Adolescents Before and During the COVID-19 Pandemic: Cross-sectional Survey Study.

BACKGROUND: The COVID-19 pandemic has resulted in significant changes to adolescents' daily lives and, potentially, to their mental health. The pandemic has also disproportionately affected historically marginalized and at-risk communities, including people of color, socioeconomically disadvantaged people, people identifying as female, and youth. OBJECTIVE: This study aimed to understand differences in depression and anxiety among 2 groups of adolescents in the United States before and during the COVID-19 pandemic, and to examine demographic and daily activity variables associated with depression and anxiety. METHODS: Online surveys were distributed in 2019 and 2020. Demographic questions were asked at the time of enrollment, and included participants' age, gender, race and ethnicity, and socioeconomic status (SES). The 8-item Patient Health Questionnaire was used to assess symptoms of depression, and the 7-item Generalized Anxiety Disorder scale was used to assess symptoms of anxiety. A total of 4 pandemic-specific daily activity questions were asked only of the pandemic group. Analyses of covariance compared depression and anxiety between prepandemic and pandemic groups. Demographic and lifestyle variables were included as covariates. RESULTS: The sample comprised a total of 234 adolescents, with 100 participants in the prepandemic group and 134 participants in the pandemic group. Within the pandemic group, 94% (n=126) of adolescents reported being out of school due to the pandemic, and another 85.8% (n=115) and 57.1% (n=76) were prevented from extracurricular activities and exercise, respectively. Higher depression was seen in the pandemic group, with a least-squares adjusted mean of 7.62 (SD 1.36) compared to 6.28 (SD 1.42) in the prepandemic group, although the difference was not significant (P=.08). There was no significant difference in anxiety scores between the 2 groups (least-squares adjusted means 5.52, SD 1.30 vs 5.01, SD 1.36; P=.48). Within the pandemic group, lower SES was predictive of anxiety, such that those in the pandemic group of lower SES were more anxious than their higher-SES peers (least-squares adjusted means 11.17, SD 2.34 vs 8.66, SD 2.16; P=.02). Within the pandemic group, being out of work or school and not partaking in extracurricular activities or exercise due to the pandemic were not associated with higher depression or anxiety scores. CONCLUSIONS: In this study, neither being in the pandemic group nor experiencing changes in daily activity due to the pandemic was associated with higher depression or anxiety. However, we found that adolescents from lower SES backgrounds experienced significantly more anxiety during the pandemic than their more privileged peers. Both instrumental and mental health interventions for low-income adolescents are imperative.

Effect of a Family Media Use Plan on Media Rule Engagement Among Adolescents: A Randomized Clinical Trial.

Importance: The American Academy of Pediatrics recommends that all families use a family media use plan to select and engage with media rules. To date, the effectiveness of this tool in promoting adolescent media rule engagement is unknown. Objective: To test the effect of a family media use plan on media rule engagement in adolescents. Design, Setting, and Participants: This randomized clinical trial with parallel design used the online Qualtrics platform for recruitment, data collection, and intervention delivery. Parents and their children (aged 12 to 17 years) who spoke and read in the English language were recruited, enrolled, and randomized to either the intervention or control group. Parent-adolescent dyads in both groups completed baseline surveys individually, and the dyads in the intervention group completed the family media use plan survey. Baseline recruitment was conducted from April 8, 2019, to May 1, 2019, and follow-up surveys were completed between June 11, 2019, and July 2, 2019. Interventions: The American Academy of Pediatrics family media use plan. Main Outcomes and Measures: The primary outcome was media rule engagement reported by adolescents. Media rules were extracted from the family media use plan, and adolescents rated each rule (using Likert scales) according to whether the rule was present or followed in their home. Secondary outcomes were adolescent-perceived technology importance and changes in sleep, physical activity, and depression. Results: A total of 1520 parent-adolescent dyads were enrolled in the trial and randomized to either the intervention or control group. Adolescents had a mean (SD) age of 14.5 (1.6) years, and 789 were female (51.9%) and 1027 were White (67.6%) individuals. Parents had a mean (SD) age of 44.1 (8.5) years, and 995 were women (65.5%) and 1021 were White individuals (67.2%). For media rule engagement, the between-group difference was -0.1 (95% CI, -1.1 to 0.9). Conclusions and Relevance: This randomized clinical trial found that completing a family media use plan did not lead to statistically significant changes in media rule engagement for adolescents in the intervention group. Future studies should consider revising the family media use plan and exploring the importance of technology as an intervention outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03881397.

Resident Workshop to Improve Inpatient Documentation Using the Progress Note Assessment and Plan Evaluation (PNAPE) Tool.

Introduction: Physicians enter residency with varied knowledge regarding the purpose of progress notes and proficiency writing them. The objective of this study was to test whether resident knowledge, beliefs, and confidence writing inpatient progress notes improved after a 2.5-hour workshop intervention. Methods: An educational workshop and note assessment tool was constructed by resident and faculty stakeholders based on a review of literature and institutional best practices. The Progress Note Assessment and Plan Evaluation (PNAPE) tool was designed to assess adherence to best practices in the assessment and plan section of progress notes. Thirty-four residents from a midsized pediatric residency program attended the workshop, which consisted of didactics and small-group work evaluating sample notes using the PNAPE tool. Participants completed a four-question online pre- and postworkshop survey to evaluate their knowledge of progress note components and attitudes regarding note importance. Pre-post analysis was performed with Chi-square testing for true/false questions, and Mann-Whitney testing for Likert scale questions and summative scores. Results: A majority of pediatric residents completed the preintervention (n = 26, 76% response rate) and postintervention (n = 23, 68% response rate) surveys. Accurate response rate improved in 15 of 20 of the true/false items, with a statistically significant improvement in five items. Resident perceptions of note importance and confidence in note writing also increased. Discussion: A workshop intervention may effectively educate pediatric residents about progress note best practices. Further studies should assess the impact of the intervention on sustained knowledge and beliefs about progress notes and subsequent note quality.

Simultaneous assessment of aberrant retinal vascularization, thickness, and function in an in vivo mouse oxygen-induced retinopathy model.

BACKGROUND: Retinopathy of prematurity is a condition of abnormal retinal vascularization in premature infants. The effect of abnormal vascularization on retinal structure and function is unclear. In vivo studies of retinal vascularization, thickness, and function were performed in mice with oxygen-induced retinopathy (OIR mice). METHODS: Eighteen mice were exposed to hyperoxia at postnatal day (P) 7, whereas 18 mice were raised in room air (RA). At P20 and 40, electroretinogram was performed for a-wave and b-wave amplitudes and peak times, followed by simultaneous fluorescein angiography for retinal avascular area, arterial tortuosity, and vein dilation assessments, and spectral domain optical coherence tomography for retinal thickness. RESULTS: Capillary density appeared sparser in OIR mice, but retinal avascular area similar to RA mice. Retinal artery tortuosity was higher at P20 and P40 (P = 0.0001) in OIR than RA mice. OIR mice had dilated retinal veins at P20 and thinner inner retinas at P40. Retinal vein width positively correlated with inner retinal thickness (P = 0.008). b-wave amplitude was decreased in avascular retinal areas, and correlated with inner retinal thinning. b-wave peak time was prolonged in adult OIR mice at high intensities (P = 0.03). CONCLUSIONS: Focal variations in retinal vascularization of OIR mice correlate with thickness and function. Adult OIR mice had increased retinal artery tortuosity, prolonged b-wave peak time, and decreased retinal vein width with inner retina attrition. These suggest abnormalities in inner retinal morphology or post-receptor signaling. Studying interactions between retinal vascular, structural, and functional changes could enhance knowledge of OIR pathogenesis and potential therapies.

Response-to-repeatability of quantitative imaging features for longitudinal response assessment.

Quantitative imaging biomarkers (QIBs) are often selected and ranked based on their repeatability performance. In the context of treatment response assessment, however, one must also consider how sensitive a QIB is to measuring changes in the tumour. This work introduces response-to-repeatability ratio (R/R), which weighs the ability of a QIB to detect significant changes with respect to its measurement repeatability and applies it to the case of PET texture features. R/R is evaluated as the proportion of measurable changes from baseline to follow-up for each candidate QIB. We analyse 47 texture features extracted from lesions in bone-metastatic prostate cancer patients who received double baseline and/or baseline to treatment follow-up 18F-NaF PET/CT scans. R/R evaluates the proportion of follow-up changes outside of the 95% limits of agreement (LOA) defined by test-retest values. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) are calculated for each feature. Relationship between ICC and R/R are evaluated with the Spearman's correlation coefficient. R/R varied significantly across texture features: 41/47 (87%) features demonstrated R/R > 5%; 21/47 (45%) features demonstrated R/R > 10%, and 11/47 (23%) features demonstrated R/R > 20%. LOA of features ranged from [0.998, 1.001] to [0.22, 4.86]. Repeatability alone did not qualify a feature for its efficacy at detecting measurable change at follow-up, as shown by weak correlations between R/R and both CV and ICC (ρ = 0.23 and ρ = 0.40, respectively). Three features demonstrated excellent ICC (ICC > 0.75) and R/R greater than that of SUVmax (R/R = 41.8%): skewness (ICC = 0.92, R/R = 75.4%), kurtosis (ICC = 0.88, R/R = 47.0%) and diagonal moment (ICC = 0.88, R/R = 45.5%). R/R characterizes the sensitivity of candidate QIBs to detect measurable changes at follow-up. R/R supplements existing precision performance metrics (e.g. CV, ICC, and LOA) as an index to assess the utility of QIBs for response assessment.

Quantitative Assessment of Early [18F]Sodium Fluoride Positron Emission Tomography/Computed Tomography Response to Treatment in Men With Metastatic Prostate Cancer to Bone.

Purpose [18F]Sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) is a promising radiotracer for quantitative assessment of bone metastases. This study assesses changes in early NaF PET/CT response measures in metastatic prostate cancer for correlation to clinical outcomes. Patients and Methods Fifty-six patients with metastatic castration-resistant prostate cancer (mCRPC) with osseous metastases had NaF PET/CT scans performed at baseline and after three cycles of chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 40). A novel technology, Quantitative Total Bone Imaging, was used for analysis. Global imaging metrics, including maximum standardized uptake value (SUVmax) and total functional burden (SUVtotal), were extracted from composite lesion-level statistics for each patient and tracked throughout treatment. Progression-free survival (PFS) was calculated as a composite end point of progressive events using conventional imaging and/or physician discretion of clinical benefit; NaF imaging was not used for clinical evaluation. Cox proportional hazards regression analyses were conducted between imaging metrics and PFS. Results Functional burden (SUVtotal) assessed midtreatment was the strongest univariable PFS predictor (hazard ratio, 1.97; 95% CI, 1.44 to 2.71; P < .001). Classification of patients based on changes in functional burden showed stronger correlation to PFS than did the change in number of lesions. Various global imaging metrics outperformed baseline clinical markers in predicting outcome, including SUVtotal and SUVmean. No differences in imaging response or PFS correlates were found for different treatment cohorts. Conclusion Quantitative total bone imaging enables comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden assessed after three cycles of hormonal therapy or chemotherapy was predictive of PFS for men with mCRPC. This supports ongoing development of NaF PET/CT-based imaging biomarkers in mCRPC to bone.

Evaluation of a pharmacist-led pilot service based on the anticholinergic risk scale.

OBJECTIVES: To determine primary care physician (PCP) acceptance rates of electronic medication therapy recommendations based on anticholinergic burden for high-risk elderly patients, and to evaluate potential associations between recommendation acceptance and patient-provider characteristics. SETTING: Two medical clinics within Dean Health System, an integrated health care organization comprising ambulatory surgery centers, medical clinics, community pharmacies, specialty pharmacies, a health plan, and a pharmacy benefits management company. PRACTICE INNOVATION: In this pilot service, the medical records of patients at least 60 years old who met the following criteria were evaluated bimonthly: 1) PCP visit within 2 weeks; (2) three or more inpatient hospitalizations or emergency department visits in the past year; and (3) ten or more active medications. Anticholinergic Risk Scale (ARS) scores of eligible patients were calculated, and medication therapy recommendations were sent electronically to PCPs for patients with an ARS score greater than 3. Post-visit recommendation outcomes were recorded. EVALUATION: Descriptive statistics were utilized to characterize patients, physicians, and recommendations. A generalized linear mixed effects model with physician specific random effects was employed to evaluate recommendation acceptance rates, and odds ratios were calculated to quantify associations between baseline patient/provider characteristics and the likelihood of recommendation acceptance. Changes in aggregate ARS scores were evaluated with the use of a paired t test. RESULTS: Fifty-nine patients were included in this pilot, with 89 medication therapy recommendations made to 21 PCPs. An overall recommendation acceptance rate of 50% (95% confidence interval [CI] 37%-63%) was observed. There were no significant associations identified between baseline patient/provider characteristics and medication recommendation acceptance. CONCLUSION: High recommendation acceptance rates were achieved with the combination of objective anticholinergic risk assessment and algorithm-driven medication therapy recommendations. The lack of identified associations between patient/provider characteristics and recommendation acceptance supports the future scalability of this novel service.

Medical Complexity among Children with Special Health Care Needs: A Two-Dimensional View.

OBJECTIVE: To identify subgroups of U.S. children with special health care needs (CSHCN) and characterize key outcomes. DATA SOURCE: Secondary analysis of 2009-2010 National Survey of CSHCN. STUDY DESIGN: Latent class analysis grouped individuals into substantively meaningful classes empirically derived from measures of pediatric medical complexity. Outcomes were compared among latent classes with weighted logistic or negative binomial regression. PRINCIPAL FINDINGS: LCA identified four unique CSHCN subgroups: broad functional impairment (physical, cognitive, and mental health) with extensive health care (Class 1), broad functional impairment alone (Class 2), predominant physical impairment requiring family-delivered care (Class 3), and physical impairment alone (Class 4). CSHCN from Class 1 had the highest ED visit rates (IRR 3.3, p < .001) and hospitalization odds (AOR: 12.0, p < .001) and lowest odds of a medical home (AOR: 0.17, p < .001). CSHCN in Class 3, despite experiencing more shared decision making and medical home attributes, had more ED visits and missed school than CSHCN in Class 2 (p < .001); the latter, however, experienced more cost-related difficulties, care delays, and parents having to stop work (p < .001). CONCLUSIONS: Recognizing distinct impacts of cognitive and mental health impairments and health care delivery needs on CSHCN outcomes may better direct future intervention efforts.

A Quantitative Study of Triggered Palliative Care Consultation for Hospitalized Patients With Advanced Cancer.

CONTEXT: Unplanned cancer-related hospital admissions often herald entry into the final phase of life. Hospitalized patients with advanced cancer have a high symptom burden and a short life expectancy, which may warrant palliative care intervention. OBJECTIVES: To identify the impact of implementing triggered palliative care consultation (TPCC) as part of standard care for patients admitted to the solid-tumor oncology service with advanced cancer. METHODS: We conducted a prospective, sequential, three-cohort study to evaluate TPCC feasibility and impact using patient-reported outcomes, electronic medical records to identify resource utilization, and surveys of oncologists' perspectives on TPCC. RESULTS: Sixty-five patients were evaluated before TPCC implementation (Cohort 1). Seventy patients (Cohort 2) were evaluated after initiation of TPCC, and 68 patients (Cohort 3) were evaluated after modifications based on implementation barriers identified in Cohort 2. The percentage of patients correctly identifying their cancer as incurable increased from 65% in Cohort 1 to 94% in Cohorts 2 and 3. TPCC had minimal impact on hospice utilization, cost of care, survival, patient-reported symptoms, and patient satisfaction, likely because of the limited nature of the intervention. Implementation was challenging, with only 60% of patients in Cohort 2 and 62% in Cohort 3 receiving TPCC. Overall, the intervention was viewed favorably by 74% of oncologists. CONCLUSION: Although TPCC was viewed favorably, implementation was logistically challenging because of short stays, high-acuity symptoms, and individual provider resistance. TPCC improved patients' understanding of their cancer. This population demonstrates high palliative care needs, warranting further research into how best to deliver care.

Genetic counseling graduate student debt: impact on program, career and life choices.

The cost of education is rising, increasing student financial aid and debt for students pursuing higher education. A few studies have assessed the impact of student debt in medicine, physical therapy and social work, but little is known about the impact of student debt on genetic counseling students and graduates. To address this gap in knowledge, a web-based study of 408 recent alumni of genetic counseling programs in North America was conducted to assess the impact of student debt on program, career and life choices. Over half (63 %; n = 256/408) of the participants reported that loans were extremely important in their ability to attend their training program, with most using subsidized loans no longer available to current graduate students. While participants were generally satisfied with their genetic counseling education, 83 % (n = 282/342) of participants with student debt reported feeling burdened by their debt, which had a median of $40,000-$50,000. This debt is relatively close to the median starting salary reported by survey participants ($45,000-$50,000), breaching the "20-10 rule" that states student debt should not exceed 20 % of annual net income. In response to this critical issue, we propose recommendations for the genetic counseling field that may help alleviate student debt impact and burden.

Assessment of guilt and shame in patients with non-small-cell lung cancer compared with patients with breast and prostate cancer.

PURPOSE: Patients with lung cancer might feel more guilt and shame resulting from previous smoking. This study was designed to determine the levels of guilt and shame among patients with non-small-cell lung cancer (NSCLC) compared with breast and prostate cancer. PATIENTS AND METHODS: Surveys were sent to participants 3 times (at enrollment, 2 months, and 6 months). Patients were eligible if they had stage IV NSCLC, breast cancer, or prostate cancer. The survey included tests of generalized guilt, shame, depression, and anxiety as well as guilt, shame, and embarrassment related to one's cancer. RESULTS: One hundred seventy-two participants completed >or= 1 questionnaire: 96 patients with NSCLC, 30 patients with breast cancer, and 46 patients with prostate cancer. Of the patients with NSCLC, 91.7% were current or former smokers versus 67.1% of the comparison patients. A composite score of embarrassment related to one's cancer (perceived cancer-related stigma; PCRS) was higher in patients with NSCLC (P < .01). Mean baseline generalized guilt and shame scores were not different among groups and did not change over time. A history of smoking correlated with increased levels of guilt and shame, regardless of tumor type. A personal identification of past behaviors as contributing to cancer correlated with higher levels of guilt, shame, anxiety, and depression. Of the patients with NSCLC, 29.5% felt that their behaviors contributed to their cancer compared with 10.5% of the comparison patients. CONCLUSION: Patients with NSCLC had higher levels of PCRS than patients with prostate cancer or breast cancer but not higher baseline levels of shame and guilt. Smoking is correlated with higher levels of guilt and shame. A belief that one caused one's own cancer is correlated with higher levels of guilt, shame, anxiety, and depression. These findings could be translated into an increased need for open communication among patients and their providers surrounding issues of cancer causation, guilt, shame, depression, and anxiety.

Measuring aerobic cycling power as an assessment of childhood fitness.

The emergence of obesity, insulin resistance, and type 2 diabetes in children requires a rational, effective public health response. Physical activity remains an important component of prevention and treatment for obesity, type 2 diabetes, and insulin resistance. Studies in adults show cardiovascular fitness to be more important than obesity in predicting insulin resistance. We recently demonstrated that a school-based fitness intervention in children who are overweight could improve cardiovascular fitness, body composition, and insulin sensitivity, but it remains unclear whether accurate assessment of fitness could be performed at the school or outside of an exercise laboratory. To determine whether new methodology using measurement of cycling power could estimate cardiovascular aerobic fitness (as defined by VO2max) in middle school children who were overweight. Thirty-five middle school children (mean age 12 +/- 0.4 years) who were overweight underwent testing on a power sensor-equipped Cycle Ops indoor cycle (Saris Cycling Group, Fitchburg, WI) as well as body composition by dual x-ray absorptiometry and VO2max by treadmill determination. Insulin sensitivity was also estimated by fasting glucose and insulin. Maximal heart rate (MHR) was determined during VO2max testing, and power produced at 80%MHR was recorded. Spearman's rank correlation was performed to evaluate associations. Mean power determined on the indoor cycle at 80% of MHR was 129 +/- 77 watts, and average power at 80% MHR divided by total body weight was 1.5 +/- 0.5. A significant correlation between watts and total body weight was seen for VO2max (P = 0.03), and significant negative correlation was seen between watts/total body weight and fasting insulin (P < 0.05). Among middle school children who were overweight, there was a significant relationship between the power component of fitness and cardiovascular aerobic fitness (measured by VO2max). This more accessible and less intimidating field-based measure of power may prove useful in predicting changes in cardiovascular fitness. Thus, accurate assessment of childhood aerobic fitness may be achievable by measurement of power, possibly within the school environment, at substantially less cost and effort than laboratory-based measurements.

Placebo effect-adjusted assessment of quality of life in placebo-controlled clinical trials.

Quality of life (QoL) has become an accepted and widely used endpoint in clinical trials. The analytical tools used for QoL evaluations in clinical trials differ from those used for the more traditional endpoints, such as response to disease, overall survival or progression-free survival. Since QoL assessments are generally performed on self-administered questionnaires, QoL endpoints are more prone to a placebo effect than traditional clinical endpoints. The placebo effect is a well-documented phenomenon in clinical trials, which has led to dramatic consequences on the clinical development of new therapeutic agents. In order to account for the placebo effect, a multivariate latent variable model is proposed, which allows for misclassification in the QoL item responses. The approach is flexible in the sense that it can be used for the analysis of a wide variety of multi-dimensional QoL instruments. For statistical inference, maximum likelihood estimates and their standard errors are obtained using a Monte Carlo EM algorithm. The approach is illustrated with analysis of data from a cardiovascular phase III clinical trial.

Measuring aerobic cycling power as an assessment of childhood fitness.

The emergence of obesity, insulin resistance (IR), and type-2 diabetes (T2DM) in children requires a rational, effective public health response. Physical activity remains an important component of prevention and treatment for obesity, T2DM, and IR. Studies in adults show cardiovascular fitness (CVF) to be more important than obesity in predicting IR. We recently demonstrated that a school-based fitness intervention in children who were overweight can improve cardiovascular fitness, body composition, and insulin sensitivity, but it remains unclear whether accurate assessment of fitness could be performed at the school or outside of an exercise laboratory. The purpose of the study was to determine if a new methodology using measurement of cycling power could estimate cardiovascular aerobic fitness (as defined by maximum oxygen consumption; VO(2)max) in middle school children who were overweight. Thirty-five middle school children who were overweight (mean age 12 +/- 0.4 years) underwent testing on a power sensor- equipped Cycle Ops Indoor Cycle (IC), as well as body composition by dual x-ray absorptiometry (DXA), and VO(2)max by treadmill determination. Insulin sensitivity was also estimated by fasting glucose and insulin. Maximal heart rate (MHR) was determined during VO(2)max testing, and power produced at 80% of MHR was recorded. Spearman's rank correlation was performed to evaluate associations. Mean power determined on the IC at 80% of MHR was 129 +/- 77 watts, and average power at 80% MHR divided by total body weight (TBW) was 1.5 +/- 0.5. A significant correlation between watts/TBW was seen for VO(2)max (ml/kg/min) (p = 0.03), and significant negative correlation was seen between watts/TBW and fasting insulin (p < 0.05). In middle-school children who were overweight, there was a significant relationship between the power component of fitness and cardiovascular aerobic fitness (measured by VO(2)max). This more accessible and less intimidating field-based measure of power may prove useful in predicting changes in cardiovascular fitness. Thus, accurate assessment of childhood aerobic fitness may be achievable by measurement of power, possibly within the school environment at substantially less cost and effort than laboratory-based measurements.

Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer.

Self-expanding metal stents versus plastic prostheses in the palliation of malignant dysphagia: long-term outcome of 153 consecutive patients.

BACKGROUND: Malignant dysphagia due to esophagogastric cancer is associated with poor overall prognosis. Placements of self-expandable metal stents or plastic tubes are established methods as palliative treatment options. As an alternative and/or complementary therapy, radiologic techniques (external beam radiation/brachytherapy) and locally endoscopic techniques (laser, APC-beamer, PDT) are often used. STUDY AND GOALS: Retrospective trial of 153 patients treated in our department between 1993 and 2001. Forty-five patients received a plastic tube (Group A) and 108 patients were treated with metal stents (Group B). Both groups were compared for improvement of dysphagia score, survival, recurrent dysphagia and complications. RESULTS: Stent placement was successful in 41 of 45 (93%) patients of Group A and 107 of 108 (99%) of Group B. The median dysphagia score improved significantly in Group A (from 3.03 to 1.55, P = 0.010) and Group B (from 2.77 to 1.44, P = 0.009). Recurrent dysphagia was noted in 12 of 45 (27%) patients of Group A and 27 of 108 (25%) patients of Group B. Median survival time after stent insertion was 78 days (Group A) and 113 days (Group B). Overall complications occurred in 15 of 45 (33%) patients of Group A and 28 of 108 (26%) patients of Group B. However, significantly (P = 0.05) more major complications were seen in Group A than in Group B (22% vs. 9%). CONCLUSIONS: Our results indicate a marginal clinical benefit for metal stents versus plastic tubes in malignant dysphagia in the long run. However, metal stents seem to be safer and associated with a prolonged improvement of dysphagia score.