Lipid Testing among Youth in Medicaid: The Role of Social Determinants of Health and Providers.

OBJECTIVE: To assess recent temporal trends in guideline-compliant pediatric lipid testing, and to examine the influence of social determinants of health (SDoH) and provider characteristics on the likelihood of testing in youth. STUDY DESIGN: In this observational, multiyear cross-sectional study, we calculated lipid testing prevalence by year among 268 627 12-year olds from 2015 through 2019 who were enrolled in Florida Medicaid and eligible for universal lipid screening during age 9 to 11, and 11 437 22-year olds (2017-2019) who were eligible for screening during age 17-21. We compared trends in testing prevalence by SDoH and health risk factors at two recommended ages and modeled the associations between patient characteristics and provider type on lipid testing using generalized estimating equations. RESULTS: Testing among 12-year olds remained low between 2015 through 2019 with the highest prevalence in 2015 (8.0%) and lowest in 2017 (6.7%). Screening compliance among 22-year olds was highest in 2017 (21.1%) and fell to 17.8% in 2019. Hispanics and non-Hispanic Blacks in both age groups had about 2%-3% lower testing prevalence than non-Hispanic Whites. Testing in 12-year olds was 12.3% vs 7.7% with and without obesity, and 14.4% vs 7.6% with and without antipsychotic use. Participants who saw providers who were more likely to prescribe lipid testing were more likely to receive testing (OR = 2.3, 95% CI 2.0-2.8, P < .001). CONCLUSIONS: Although lipid testing prevalence was greatest among high-risk children, overall prevalence of lipid testing in youth remains very low. Provider specialty and choices by individual providers play important roles in improving guideline-compliant pediatric lipid testing.

Stratified split sampling of electronic health records.

Although superficially similar to data from clinical research, data extracted from electronic health records may require fundamentally different approaches for model building and analysis. Because electronic health record data is designed for clinical, rather than scientific use, researchers must first provide clear definitions of outcome and predictor variables. Yet an iterative process of defining outcomes and predictors, assessing association, and then repeating the process may increase Type I error rates, and thus decrease the chance of replicability, defined by the National Academy of Sciences as the chance of "obtaining consistent results across studies aimed at answering the same scientific question, each of which has obtained its own data."[1] In addition, failure to account for subgroups may mask heterogeneous associations between predictor and outcome by subgroups, and decrease the generalizability of the findings. To increase chances of replicability and generalizability, we recommend using a stratified split sample approach for studies using electronic health records. A split sample approach divides the data randomly into an exploratory set for iterative variable definition, iterative analyses of association, and consideration of subgroups. The confirmatory set is used only to replicate results found in the first set. The addition of the word 'stratified' indicates that rare subgroups are oversampled randomly by including them in the exploratory sample at higher rates than appear in the population. The stratified sampling provides a sufficient sample size for assessing heterogeneity of association by testing for effect modification by group membership. An electronic health record study of the associations between socio-demographic factors and uptake of hepatic cancer screening, and potential heterogeneity of association in subgroups defined by gender, self-identified race and ethnicity, census-tract level poverty and insurance type illustrates the recommended approach.

Cost-Effectiveness of the Wellness Incentives and Navigation (WIN) Program.

OBJECTIVES: Promoting patient involvement in managing co-occurring physical and mental health conditions is increasingly recognized as critical to improving outcomes and controlling costs in this growing chronically ill population. The main objective of this study was to conduct an economic evaluation of the Wellness Incentives and Navigation (WIN) intervention as part of a longitudinal randomized pragmatic clinical trial for chronically ill Texas Medicaid enrollees with co-occurring physical and mental health conditions. METHODS: The WIN intervention used a personal navigator, motivational interviewing, and a flexible wellness expense account to increase patient activation, that is, the patient's knowledge, skills, and confidence in managing their self-care and co-occurring physical and mental health conditions. Regression models were fit to both participant-level quality-adjusted life years (QALYs) and total costs of care (including the intervention) controlling for demographics, health status, poverty, Medicaid managed care plan, intervention group, and baseline health utility and costs. Incremental costs and QALYs were calculated based on the difference in predicted costs and QALYs under intervention versus usual care and were used to calculate the incremental cost-effectiveness ratios (ICERs). Confidence intervals were calculated using Fieller's method, and sensitivity analyses were performed. RESULTS: The mean ICER for the intervention compared with usual care was $12 511 (95% CI $8971-$16 842), with a sizable majority of participants (70%) having ICERs below $40 000. The WIN intervention also produced higher QALY increases for participants who were sicker at baseline compared to those who were healthier at baseline. CONCLUSION: The WIN intervention shows considerable promise as a cost-effective intervention in this challenging chronically ill population.

Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.

BACKGROUND: The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. METHODS: F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14 days later, either CDDP or carboplatin was administered i.c. by CED, followed 24 h later by radiotherapy using either a synchrotron or, subsequently, megavoltage linear accelerators (LINAC). RESULTS: CDDP was administered at a dose of 3 µg in 5 µL, followed 24 h later with an irradiation dose of 15 Gy or carboplatin at a dose of 20 µg in 10 µL, followed 24 h later with 3 fractions of 8 Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180 days with 33% long term survivors (LTS) for CDDP and a MeST > 60 days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72 µg of carboplatin administered by means of Alzet® osmotic pumps over 7 days. This resulted in a MeST of > 180 days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. CONCLUSIONS: The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promising survival data ever reported using the F98 glioma model.

Assessing the reliability of the short form 12 (SF-12) health survey in adults with mental health conditions: a report from the wellness incentive and navigation (WIN) study.

BACKGROUND: Although Short Form (SF)-12 × 2® has been extensively studied and used as a valid measure of health-related quality of life in a variety of population groups, no systematic studies have described the reliability of the measure in patients with behavioral conditions or serious mental illness (SMI). METHODS AND RESULTS: We assessed the internal consistency, split-half reliability and annual test-retest correlations in a sample of 1587 participants with either a combination of physical and behavioral conditions or SMI. The Mosier's alpha was 0.70 for the Physical Composite Scale (PCS) and 0.69 for the Mental Health Composite Scale (MCS), indicating good internal consistency. We observed strong correlations between physical functioning, physical role and body pain scales (r = 0.55-0.56), and between social functioning, emotional role, and mental health (r = 0.53-0.58). We calculated split-half reliabilities to be 0.74 for physical functioning, 0.75 for physical role, 0.73 for emotional role and 0.65 for mental health respectively. We assessed the annual test-retest correlation using intraclass correlation (ICC) and found an ICC of 0.61 for PCS and 0.57 for MCS composite scores, adjusting for age, sex, race/ethnicity, and CRG. We found no decline in the correlations between baseline and the following study years until year 3. CONCLUSIONS: Our results encourage using SF-12v2® to assess health-related quality of life in the Medicaid population with combined physical and behavioral conditions or similar cohorts. TRIAL REGISTRATION: The WIN study was registered with clinicaltrials.gov on April 22, 2015. TRIAL REGISTRATION NUMBER: NCT02440906 . Retrospectively registered.

Perceptions of patients and providers on myocardial perfusion imaging for asymptomatic patients, choosing wisely, and professional liability.

BACKGROUND: Despite efforts by professional societies to reduce low value care, many reports indicate that unnecessary tests, such as nuclear myocardial perfusion imaging (MPI), are commonly used in contemporary practice. The degree to which lack of awareness and professional liability concerns drive these behaviors warrants further study. We sought to investigate patient and provider perceptions about MPI in asymptomatic patients, the Choosing Wisely (CW) campaign, and professional liability concerns. METHODS: We administered an anonymous, paper-based survey with both discrete and open-response queries to subjects in multiple outpatient settings at our facilities. The survey was completed by 456 respondents including 342 patients and 114 physicians and advanced practice providers between May and August 2014. Our outcome was to compare patient and provider perceptions about MPI in asymptomatic patients and related factors. RESULTS: Patients were more likely than providers to report that MPI was justified for asymptomatic patients (e.g. asymptomatic with family history of heart disease 75% versus 9.2%, p < 0.0001). In free responses to the question "What would be an inappropriate reason for MPI?" many responses echoed the goals of CW (for example, "If you don't have symptoms", "If the test is too risky", "For screening or in asymptomatic patients"). A minority of providers were aware of CW while even fewer patients were aware (37.2% versus 2.7%, p < 0.0001). Over one third of providers (38.9%) admitted to ordering MPI out of concern for professional liability including 48.3% of VA affiliated providers. CONCLUSIONS: While some patients and providers are aware of the low value of MPI in patients without symptoms, others are enthusiastic to use it for a variety of scenarios. Concerns about professional liability likely contribute, even in the VA setting. Awareness of the Choosing Wisely campaign is low in both groups.

Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. METHODS: CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. RESULTS: Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P < .001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P < .008), AIx (32 ± 6.6 vs 27 ± 6.6%, P < .003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P < .02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P < .008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P < .04). CONCLUSIONS: Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation.

UNLABELLED: Endothelial dysfunction is highly prevalent and associated with adverse outcomes among patients without obstructive coronary artery disease (CAD). Angiotensin II inhibition may improve endothelial function, but with continued treatment, "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone blockade further improves endothelial function. METHODS: In a double-blind, parallel-group, repeated-measures study, women with symptoms and signs of ischemia, no significant CAD, and coronary endothelial dysfunction receiving an angiotensin-converting enzyme inhibitor or receptor blocker were randomized to aldosterone blockade or placebo. The primary outcome at 16 weeks was percent change in coronary diameter to acetylcholine, and secondary outcome, coronary flow reserve to adenosine, both adjusted for baseline reactivity. RESULTS: Forty-one women completed the treatment period with repeat coronary reactivity testing. Their mean age was 54 ± 10 years; body mass index, 30 ± 7.4 kg/m2; 12% had diabetes; and 15% had metabolic syndrome. There were no significant differences between treatment groups. At baseline, the percent change in reference vessel coronary diameter to acetylcholine was -5.0% in the aldosterone blockade group and -3.4% in the placebo group and, at 16 weeks, -7.2% in the aldosterone blockade group versus -14.3% in the placebo group (P = .15). At 16 weeks, the change in coronary flow reserve to intracoronary adenosine was -0.13 in the aldosterone blockade group versus -0.25 in the placebo group (P = .66). CONCLUSION: Adding aldosterone receptor blockade to angiotensin II inhibition did not improve coronary endothelial or microvascular function among women with signs and symptoms of ischemia in the setting of nonobstructive CAD.

Drug-eluting stents may not reduce target lesion revascularization in cardiac allograft vasculopathy.

OBJECTIVE: Although drug-eluting stent (DES) compared with bare metal stent (BMS) use reduces in-stent restenosis (ISR) in traditional coronary artery disease, its efficacy in cardiac allograft vasculopathy (CAV) has not been clearly established. BACKGROUND: CAV is a leading cause of mortality after the first year following cardiac transplantation. CAV treatment options are limited, and DES use has increased significantly in this population. METHODS: In a retrospective study of heart transplant patients at our institution who underwent percutaneous coronary intervention with a BMS or DES for CAV, we compared baseline characteristics, clinical outcomes, ISR, and target lesion revascularization (TLR). The primary end-point was angiographic ISR assessed by quantitative coronary angiography analyzed as both a binary (≤50% vs. >50%) and continuous variable (follow-up minimal luminal area [MLA]/baseline MLA). Secondary outcomes included TLR and a composite of death, myocardial infarction, heart failure, and retransplantation. RESULTS: In 45 patients with DES, BMS, or both, ISR assessed as a continuous variable was statistically different between the 2 stent groups (follow-up MLA/baseline MLA = 0.796 DES vs. 0.481 BMS; P = 0.0037). There was also a significant difference in ISR (10.8% for DES versus 30.7% for BMS) when assessed as a binary variable. There was no statistically significant difference in TLR or composite cardiovascular outcomes between groups when adjusted for traditional cardiovascular risk factors. CONCLUSIONS: ISR assessed as a continuous variable was significantly different between stent groups. However, this did not lead to a difference in TLR or cardiovascular outcomes. This hypothesis-generating finding suggests that patients with CAV may not necessarily need treatment with DES, which can be more costly and carries more potential risk than BMS.

North-Central Florida Clinicians' Human Papillomavirus Vaccine Recommendation Priorities and Practices for 11- to 12-Year-Olds: A Discrete Choice Experiment.

PURPOSE: Within the United States, human papillomavirus (HPV) vaccination rates remain low. We examined HPV vaccine recommendation practices among Florida clinicians by assessing variability in: (1) recommendation priorities by patient characteristics and (2) concordance with best practices. METHODS: In 2018 and 2019, we conducted a cross-sectional survey incorporating a discrete choice experiment among primary care clinicians (MD/DO, APRN, and PA). We used linear mixed-effects models to determine the importance of patient characteristics (age, sex, time in practice, and chronic condition) and parental concerns. We compared clinician endorsement of predetermined constructs with reported vaccine recommendation statements. RESULTS: Among 540 surveys distributed, 272 were returned and 105 reported providing preventive care to 11- to 12-year-olds (43% response rate). Among completing clinicians, 21/99 (21%) did not offer the HPV vaccine. Among clinicians offering the vaccine (n = 78), 35%-37% of each decision to recommend the vaccine was based on the child's age (15 vs. 11 years). For closed-ended questions, most clinicians endorsed best practices including emphasizing cancer prevention (94% for girls and 85% for boys; p = .06), vaccine efficacy (60% both sexes), safety (58% girls and 56% boys), importance at 11-12 years (64% both sexes), and bundling vaccines (35% girls and 31% boys). When clinicians reported their typical recommendation, fewer clinicians incorporated best practices (59% cancer prevention, 5% safety, 8% the importance at 11-12 years, and 8% bundling vaccines). DISCUSSION: HPV vaccination recommendation strategies among Florida clinicians somewhat aligned with best practices. Alignment was higher when clinicians were explicitly asked to endorse constructs versus provide recommendations.

Synthesis, biological evaluation, and radioiodination of halogenated closo-carboranylthymidine analogues.

The synthesis and initial biological evaluation of 3-carboranylthymidine analogues (3CTAs) that are (radio)halogenated at the closo-carborane cluster are described. Radiohalogenated 3CTAs have the potential to be used in the radiotherapy and imaging of cancer because they may be selectively entrapped in tumor cells through monophosphorylation by human thymidine kinase 1 (hTK1). Two strategies for the synthesis of a (127)I-labeled form of a specific 3CTA, previously designated as N5, are described: (1) direct iodination of N5 with iodine monochloride and aluminum chloride to obtain N5-(127)I and (2) initial monoiodination of o-carborane to 9-iodo-o-carborane followed by its functionalization to N5-(127)I. The former strategy produced N5-(127)I in low yields along with di-, tri-, and tetraiodinated N5 as well as decomposition products, whereas the latter method produced only N5-(127)I in high yields. N5-(127)I was subjected to nucleophilic halogen- and isotope-exchange reactions using Na(79/81)Br and Na(125)I, respectively, in the presence of Herrmann's catalyst to obtain N5-(79/81)Br and N5-(125)I, respectively. Two intermediate products formed using the second strategy, 1-(tert-butyldimethylsilyl)-9-iodo-o-carborane and 1-(tert-butyldimethylsilyl)-12-iodo-o-carborane, were subjected to X-ray diffraction studies to confirm that substitution at a single carbon atom of 9-iodo-o-carborane resulted in the formation of two structural isomers. To the best of our knowledge, this is the first report of halogen- and isotope-exchange reactions of B-halocarboranes that have been conjugated to a complex biomolecule. Human TK1 phosphorylation rates of N5, N5-(127)I, and N5-(79/81)Br ranged from 38.0% to 29.6% relative to that of thymidine, the endogenous hTK1 substrate. The in vitro uptake of N5, N5-(127)I, and N5-(79/81)Br in L929 TK1(+) cells was 2.0, 1.8, and 1.4 times greater than that in L929 TK1(-) cells.

Florida Medicaid Children's Receipt of First-Line Psychosocial Care Prior to Antipsychotic Initiation.

BACKGROUND AND OBJECTIVE: First-line, nonpharmacological therapy is recommended for many pediatric mental health (MH) conditions prior to initiating antipsychotic prescription therapies. Many children do not receive these recommended services, despite the known association between antipsychotic medications and metabolic dysfunction. The main objective of this study was to quantify the association among children's MH diagnosis categories, sociodemographic characteristics and receipt of first-line psychosocial care among children in Florida Medicaid METHODS: Florida Medicaid enrollment, healthcare and pharmacy claims were used for this multivariate analysis. Children were assigned to condition clusters wherein related diagnoses were grouped into clinically relevant categories. A total of 7704 children were included in the final analysis. RESULTS: Twenty-four percent of children in Florida Medicaid do not receive first-line, nonpharmacological psychosocial care. Age was significantly associated with not receiving psychosocial services, with older children less likely to receive. Non-Hispanic White children as well as those living in rural areas had lower odds of receiving behavioral intervention prior to initiating antipsychotics. Children with mood-disorders, behavior problems, anxiety and stress related disorders were more likely to receive first-line psychosocial care. CONCLUSIONS: This study provides an important understanding of the variability in receipt of first-line psychosocial care before antipsychotic medication initiation among children in Medicaid based on sociodemographic and MH health characteristics. These analyses can be used to develop quality improvement initiatives targeted toward children that are most vulnerable for not receiving recommended care.

Enhancing Quality Measurement With Clinical Information: A Use Case of Body Mass Index Change Among Children Taking Second Generation Antipsychotics.

OBJECTIVE: We sought to examine the extent to which body mass index (BMI) was available in electronic health records for Florida Medicaid recipients aged 5 to 18 years taking Second-Generation Antipsychotics (SGAP). We also sought to illustrate how clinical data can be used to identify children most at-risk for SGAP-induced weight gain, which cannot be done using process-focused measures. METHODS: Electronic health record (EHR) data and Medicaid claims were linked from 2013 to 2019. We quantified sociodemographic differences between children with and without pre- and post-BMI values. We developed a linear regression model of post-BMI to examine pre-post changes in BMI among 4 groups: 1) BH/SGAP+ children had behavioral health conditions and were taking SGAP; 2) BH/SGAP- children had behavioral health conditions without taking SGAP; 3) children with asthma; and 4) healthy children. RESULTS: Of 363,360 EHR-Medicaid linked children, 18,726 were BH/SGAP+. Roughly 4% of linked children and 8% of BH/SGAP+ children had both pre and post values of BMI required to assess quality of SGAP monitoring. The percentage varied with gender and race-ethnicity. The R2 for the regression model with all predictors was 0.865. Pre-post change in BMI differed significantly (P < .0001) among the groups, with more BMI gain among those taking SGAP, particularly those with higher baseline BMI. CONCLUSION: Meeting the 2030 Centers for Medicare and Medicaid Services goal of digital monitoring of quality of care will require continuing expansion of clinical encounter data capture to provide the data needed for digital quality monitoring. Using linked EHR and claims data allows identifying children at higher risk for SGAP-induced weight gain.

The effects of experimentally manipulated social status and subjective social status on physical activity among Hispanic adolescents: An RCT.

BACKGROUND: Low objective socioeconomic status (SES) and subjective social status (SSS), one's perceived social rank, are associated with obesity. This association may be due, in part, to social status-related differences in energy expenditure. Experimental studies are needed to assess the extent to which SES and SSS relate to energy expenditure. OBJECTIVE: Assess the effects of experimentally manipulated social status and SSS on moderate-to-vigorous physical activity (MVPA) and sedentary behaviour. METHODS: One hundred thirty-three Hispanic adolescents aged 15-21 were randomized to a high or low social status position, facilitated through a rigged game of Monopoly™. SSS was assessed with MacArthur Scales. Post-manipulation 24-h MVPA and sedentary behaviour were assessed via accelerometry. Analyses were conducted with general linear regression models. RESULTS: Experimentally manipulated social status did not significantly affect the total time spent in MVPA or sedentary behaviour; however, identifying as low SSS was significantly associated with less MVPA (p = 0.0060; 18.76 min less). CONCLUSIONS: Tewnty-four-hour MVPA and sedentary behaviour are not affected by an acute experimental manipulation of social status. However, low SSS, independent of SES, was associated with clinically significant differences in MVPA. SSS may be a better predictor of MVPA than SES among Hispanic adolescents, potentially influencing obesity, and other health-related outcomes.

Convection enhanced delivery of carboranylporphyrins for neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α] Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these compounds, designated H2TBP, H2TCP, and H2DCP, have been evaluated in the present study. The goals were two-fold. First, to determine their biodistribution following intracerebral (i.c.) administration by short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by Alzet™ osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. pump delivery were high and they remained so at 24 h. The corresponding normal brain concentrations were low and the blood and liver concentrations were undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITR) with H2TCP and H2TBP 24 h after CED or pump delivery. Mean survival times (MST) ± standard deviations of animals that had received H2TCP or H2TBP, followed by BNCT, were of 35 ± 4 and 44 ± 10 days, compared to 23 ± 3 and 27 ± 3 days, respectively, for untreated and irradiated controls. However, since the tumor boron concentrations of the carboranylporphyrins were 3-5× higher than intravenous (i.v.) boronophenylalanine (BPA), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed that there were large numbers of porphyrin-laden macrophages, as well as extracellular accumulations of porphyrins, indicating that the seemingly high tumor boron concentrations did not represent the true tumor cellular uptake. Nevertheless, our data are the first to show that carboranyl porphyrins can be used as delivery agents for BNCT of an experimental brain tumor. Based on these results, we now are in the process of synthesizing and evaluating carboranylporphyrins that could have enhanced cellular uptake and improved therapeutic efficacy.

Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors.

The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma. Tumor cells were implanted stereotactically into the brains of syngeneic Fischer rats, and 13 or 17 d. later carboplatin (20 µg/10 µl) was administered by either CED over 30 min or by Alzet osmotic pumps (0.5 µg/µl/h for 168 h.) beginning at 7 d after tumor implantation. Rats were irradiated with a 15 Gy fractionated dose (5 Gy × 3) of 6 MV photons to the whole brain beginning on the day after drug administration. Other groups of rats received either carboplatin or X-irradiation alone. The tumor carboplatin concentration following CED of 20 µg in 10 µl was 10.4 µg/g, which was equal to that observed following i.v. administration of 100 mg/kg b.w. Rats bearing small tumors, treated with carboplatin and X-irradiation, had a mean survival time (MST) of 83.4 d following CED and 111.8 d following pump delivery with 40% of the latter surviving >180 d (i.e. cured) compared to 55.2 d for CED and 77.2 d. for pump delivery of carboplatin alone and 31.8 d and 24.2 d, respectively, for X-irradiated and untreated controls. There was no microscopic evidence of residual tumor in the brains of all long-term survivors. Not surprisingly, rats with large tumors had much shorter MSTs. Only modest increases in MSTs were observed in animals that received either oral administration or CED of temozolomide plus X-irradiation (23.2 d and 29.3 d) compared to X-irradiation alone. The present survival data, and those previously reported by us, are among the best ever obtained with the F98 glioma model. Initially, they could provide a platform for a Phase I clinical trial to evaluate the safety and potential therapeutic efficacy of CED of carboplatin in patients with recurrent glioblastomas, and ultimately a Phase II trial of carboplatin in combination with radiation therapy.

Psychological Resilience, Experimentally Manipulated Social Status, and Dietary Intake among Adolescents.

Relative to other racial/ethnic groups in the United States, Hispanic American (HA) youth have higher rates of overweight and obesity. Previous work suggests that low perceived social status (SS) promotes excess caloric intake and, thereby, development of obesity. Psychological resilience may play a role in reducing adverse eating behaviors and risk for obesity. The objective of this study was to investigate whether resilience (as measured by the Connor Davidson Resilience Scale) interacts with experimentally manipulated SS to affect dietary intake among HA adolescents (n = 132). Using a rigged game of Monopoly (Hasbro, Inc.), participants were randomized to a high or low SS condition. Following the Monopoly game, participants consumed an ad libitum lunch and their dietary intake was assessed. There was a significant interaction between resilience and experimentally manipulated SS for total energy intake (p = 0.006), percent energy needs consumed (p = 0.005), and sugar intake (p = 0.004). For the high SS condition, for each increase in resilience score, total energy intake decreased by 7.165 ± 2.866 kcal (p = 0.014) and percent energy needs consumed decreased by 0.394 ± 0.153 (p = 0.011). In the low SS condition, sugar intake increased by 0.621 ± 0.240 g for each increase in resilience score (p = 0.011). After correction for multiple comparisons, the aforementioned interactions, but not simple slopes, were statistically significant.

Human Papillomavirus Vaccination and Human Papillomavirus-Associated Cancer Rates Within Florida Counties.

INTRODUCTION: To direct interventions, the Florida counties with the greatest risk of current and future human papillomavirus‒associated cancers were identified by estimating county-level (1) percentages of adolescents aged 13-17 years who initiated (≥1 dose) and were up to date (2-3 doses) for the human papillomavirus vaccine and (2) human papillomavirus‒associated cancer incidence rates. METHODS: Records were obtained for human papillomavirus vaccinations from the Florida immunization registry (2006-2019), incident cancer cases from the Florida registry (2013-2017), and annual population counts from the Florida Department of Health (2006-2019). In 2020, annual county-level human papillomavirus vaccine initiation, human papillomavirus vaccine up-to-date, and age-adjusted human papillomavirus‒associated cancer incidence rates were estimated. RESULTS: Among adolescents aged 13-17 years, average 2018-2019 county-specific human papillomavirus vaccine initiation ranged from 38% to 100% for females and from 34% to 96% for males. Up-to-date estimates ranged from 20% to 72% for females and from 24% to 77% for males. The majority (78%) of counties with initiation and up-to-date estimates within the lowest tercile were located in Northern Florida. County-specific 2013-2017 annualized, adjusted human papillomavirus‒associated cancer incidence rates ranged from 0 to 29.8 per 100,000 among females and from 5.4 to 24.1 per 100,000 among males. Counties within the highest tercile for human papillomavirus‒associated cancers were primarily (90% for females and 77% for males) located in Northern Florida. CONCLUSIONS: Human papillomavirus‒associated cancer risk varies widely across Florida counties, with particularly high risk within Northern Florida. Targeting interventions toward counties with low vaccination and high cancer rates may reduce human papillomavirus‒associated cancers.

Do patients at high risk for Hepatitis C receive recommended testing? A retrospective cohort study of statewide Medicaid claims linked with OneFlorida clinical data.

ABSTRACT: Hepatitis C virus (HCV) infection is a leading risk factor for hepatocellular carcinoma.We employed a retrospective cohort study design and analyzed 2012-2018 Medicaid claims linked with electronic health records data from the OneFlorida Data Trust, a statewide data repository containing electronic health records data for 15.07 million Floridians from 11 health care systems. Only adult patients at high-risk for HCV (n = 30,113), defined by diagnosis of: HIV/AIDS (20%), substance use disorder (64%), or sexually transmitted infections (22%) were included. Logistic regression examined factors associated with meeting the recommended sequence of HCV testing.Overall, 44.1% received an HCV test. The odds of receiving an initial test were significantly higher for pregnant females (odds ratio [OR]1.99; 95% confidence interval [CI] 1.86-2.12; P < .001) and increased with age (OR 1.01; 95% CI 1.00-1.01; P < .001).Among patients with low Charlson comorbidity index (CCI = 1), non-Hispanic (NH) black patients (OR 0.86; 95% CI 0.81-0.9; P < .001) had lower odds of getting an HCV test; however, NH black patients with CCI = 10 had higher odds (OR 1.41; 95% CI 1.21-1.66; P < .001) of receiving a test. Of those who tested negative during initial testing, 17% received a second recommended test after 6 to 24 months. Medicaid-Medicare dual eligible patients, those with high CCI (OR 1.14; 95% CI 1.11-1.17; P < .001), NH blacks (OR 1.93; 95% CI 1.61-2.32; P < .001), and Hispanics (OR 1.49; 95% CI 1.08-2.06; P = .02) were significantly more likely to have received a second HCV test, while pregnant females (OR 0.71; 95% CI 0.57-0.89; P = .003), had lower odds of receiving it. The majority of patients who tested positive during the initial test (97%) received subsequent testing.We observed suboptimal adherence to the recommended HCV testing among high-risk patients underscoring the need for tailored interventions aimed at successfully navigating high-risk individuals through the HCV screening process. Future interventional studies targeting multilevel factors, including patients, clinicians and health systems are needed to increase HCV screening rates for high-risk populations.

Experimentally Manipulated Low Social Status and Food Insecurity Alter Eating Behavior Among Adolescents: A Randomized Controlled Trial.

OBJECTIVE: This randomized trial experimentally manipulated social status to assess effects on acute eating behavior and 24-hour energy balance. METHODS: Participants (n = 133 Hispanics; age 15-21 years; 60.2% females) were randomized to low social status ("LOW") or high social status ("HIGH") conditions in a rigged game of Monopoly (Hasbro, Inc.). Acute energy intake in a lunchtime meal was measured by food scales. Twenty-four-hour energy balance was assessed via summation of resting metabolic rate (metabolic cart), physical activity energy expenditure (accelerometer), thermic effect of food, and subtraction of twenty-four-hour energy intake (food diary). RESULTS: In the total sample, no significant differences were observed by study condition at lunchtime. LOW females consumed a greater percent of lunchtime daily energy needs (37.5%) relative to HIGH females (34.3%); however, this difference was not statistically significant (P = 0.291). In males, however, LOW consumed significantly less (36.5%) of their daily energy needs relative to HIGH males (45.8%; P = 0.001). For 24-hour energy balance, sex differences were nearly significant (P = 0.057; LOW females: surplus +200 kcal; HIGH males: surplus +445 kcal). Food-insecure individuals consumed a nearly significant greater lunchtime percent daily energy than those with food security (40.7% vs. 36.3%; P = 0.0797). CONCLUSIONS: The data demonstrate differential acute and 24-hour eating behavior responses between Hispanic male and female adolescents in experimentally manipulated conditions of low social status.