[Show abstract][Hide abstract] ABSTRACT: Objective:
Problematic Internet use (PIU) is an emerging health concern that lacks screening measures validated for use with adolescents and young adults. This study aimed to validate the Problematic and Risky Internet Use Screening Scale (PRIUSS) for use with older adolescents and to increase its clinical utility by determining scoring guidelines and assessing the relationship between PIU and other mental health conditions.
This cross-sectional survey study took place at a large, public Midwestern university among 330 older adolescents aged 18 to 25 years. Confirmatory factor analysis and Spearman's correlations were used to assess the PRIUSS' structural and construct validity, respectively. A risk-based scoring cutoff was estimated using a Bayesian latent class modeling approach to computing a receiver operating characteristic curve.
The confirmatory factor analysis indices for the 3-factor model indicated an acceptable fit (goodness-of-fit index 0.89, root mean square error of approximation 0.07). A cutoff of 25 (sensitivity 0.80, 95% confidence interval [CI] 0.47-0.99; specificity 0.79, 95% CI 0.73-0.84) is proposed for identifying those at risk for PIU. Participants at risk for PIU were at significantly greater odds of also reporting symptoms of attention-deficit/hyperactivity disorder (odds ratio [OR] 2.36 95% CI 1.21-4.62, P = .009), depression (OR 3.25, 95% CI 1.65-6.42, P = .008), and social anxiety (OR 3.77, 95% CI 2.06-6.89, P < .000).
The PRIUSS demonstrated validity as a PIU screening instrument for adolescents and young adults. Screening for PIU may also help to identify those at high reciprocal risk for other mental health conditions.
[Show abstract][Hide abstract] ABSTRACT: Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to investigate the degree to which waist circumference (WC), body mass index (BMI), and magnetic resonance imaging (MRI)-measured abdominal fat deposition predict insulin resistance (IR) in nonobese girls of diverse racial and ethnic backgrounds.
Fifty-seven nonobese girls (12 African-American, 16 Hispanic White, and 29 non-Hispanic White girls) aged 11-14 years were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, homeostasis model of assessment (HOMA)-IR, adiponectin, leptin, sex hormone-binding globulin, high-density lipoprotein cholesterol, and triglycerides.
Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume were dependent predictors. Hispanic White girls showed significantly higher mean fasting insulin and HOMA-IR and lower sex hormone-binding globulin than non-Hispanic White girls (p < 0.01).
In nonobese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to the BMI Z-score.
Hormone Research in Paediatrics 09/2015; DOI:10.1159/000439130 · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
During October 2011-December 2012, concurrent with a statewide pertussis outbreak, 443 Bordetella parapertussis infections were reported among Wisconsin residents. We examined clinical features of patients with parapertussis and the effect of antibiotic use for treatment and prevention.
Patients with polymerase chain reaction results positive for B. parapertussis reported during October 2011-May 2012 were interviewed regarding presence and durations of pertussis-like symptoms and receipt of azithromycin treatment. Data regarding acute cough illnesses and receipt of azithromycin prophylaxis among parapertussis patient household members (HHMs) were also collected. Using multivariate repeated measures log-binomial regression analysis, we examined associations of treatment receipt by the HHM with the earliest illness onset and prophylaxis receipt among other HHMs with the presence of any secondary cough illnesses in the household.
Among 218 patients with parapertussis, pertussis-like symptoms were frequently reported. Illness durations were significantly shorter among patients with treatment initiated 0-6 days after cough onset, compared with nonrecipients (median durations: 10 vs 19 days, P = .002). Among 361 HHMs from 120 households, compared with nonrecipients, prompt prophylaxis of HHMs was associated with no secondary cough illnesses (relative risk: 0.16; 95% confidence interval, .04-.69).
Bordetella parapertussis infection causes pertussis-like illness that might be misclassified as pertussis if B. parapertussis testing is not performed. Prompt treatment might shorten illness duration, and prompt HHM prophylaxis might prevent secondary illnesses. Further study is needed to evaluate antibiotic effectiveness for preventing parapertussis and to determine risks and benefits of antibiotic use.
[Show abstract][Hide abstract] ABSTRACT: Fluoropyrimidines and oxaliplatin have demonstrated some efficacy against pancreatic adenocarcinoma, but survival remains brief. Sorafenib is an oral multikinase inhibitor which we sought to combine with a unique capecitabine and oxaliplatin regimen for pancreatic adenocarcinoma.
We performed a multicenter phase II study of sorafenib 200 mg orally twice daily along with oxaliplatin 85 mg/m(2) IV on days 1 and 15, followed by capecitabine 2250 mg/m(2) orally every 8 h for six doses starting on days 1 and 15 of a 28-day cycle in patients who had no more than one previous chemotherapy regimen for their pancreatic adenocarcinoma. The primary objective was response rate; secondary objectives were progression-free survival (PFS), overall survival (OS), and safety.
Twenty-four patients were enrolled; median age was 63 years (range 48-83). The most common related toxicities were fatigue, neuropathy, anemia, thrombocytopenia, diarrhea, nausea, leukopenia, and hand-foot syndrome. Grade 3 hand-foot syndrome was rare (4 %). Other grade 4 toxicities included abdominal pain (8 %), pulmonary embolism (4 %), and anemia (4 %). Three partial responses were seen (13 %), and 11 patients had stable disease (46 %) as their best response. Median PFS was 6.0 months (range 1.5-13 months). Median OS was 8.1 months (range 1.5-13.6 months).
Sorafenib, oxaliplatin, and capecitabine produced partial responses in patients with advanced pancreatic cancer including previously treated patients and demonstrated a PFS of 6 months with few grade 3/4 toxicities.
Cancer Chemotherapy and Pharmacology 06/2015; 76(2). DOI:10.1007/s00280-015-2783-y · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preterm birth, and its often-required medical interventions, can result in respiratory and gas exchange deficits into childhood. However, the long-term sequelae into adulthood are not well understood.
To determine exercise capacity and pulmonary gas exchange efficiency during exercise in adult survivors of preterm birth.
Preterm (n=14), very low birth weight (VLBW; <1500g) adults (20-23 years), and term-born, age-matched controls (n=16), performed incremental exercise on a cycle ergometer to volitional exhaustion while breathing normoxia (fraction of inspired oxygen (FIO2=0.21) or hypoxia (FIO2=0.12).
Ventilation, mixed expired gases, arterial blood gases, power output and V̇O2, were measured during rest and exercise. We calculated alveolar-to-arterial oxygen difference (A-aDO2) to determine pulmonary gas exchange efficiency. Preterm subjects had a lower power output at volitional exhaustion than controls in normoxia (150±10 vs 180±10W, P=0.01), despite a similar normoxic V̇O2. However, during hypoxic exercise, there was no difference in power output at volitional exhaustion between the two groups (116±10 vs 135±10W, P=0.11). Preterm subjects also exhibited a more acidotic, acid-base balance throughout exercise compared to control subjects. In contrast to other studies, adults born preterm, as a group developed a wider A-aDO2 and lower PaO2 than controls during normoxic but not during hypoxic exercise.
This study demonstrates that pulmonary gas exchange efficiency is lower in some adult survivors of preterm birth during exercise compared to controls. The gas exchange inefficiency, when present, is accompanied by low arterial blood oxygen tension. Preterm subjects also exhibit a reduced power output. Overall, our findings suggest potential long-term consequences of extreme preterm birth and very low birth weight on cardiopulmonary function.
Annals of the American Thoracic Society 06/2015; 12(8). DOI:10.1513/AnnalsATS.201410-470OC
[Show abstract][Hide abstract] ABSTRACT: Rapid disease progression associated with increased tumor proliferation has been observed during withdrawal of anti-angiogenic therapy. We characterize the dynamics of withdrawal flare for axitinib.
Thirty patients with metastatic solid malignancies received axitinib for 2 weeks, followed by a 1-week drug holiday. Twenty patients suitable for PET imaging received scans with (18)F-3'deoxy-3'fluoro-L-thymidine (FLT), a marker of proliferation. Plasma VEGF and axitinib pharmacokinetic levels were also assessed at specified time points.
During axitinib withdrawal, significant increases in both SUVmax (+22 %; p = 0.006) and SUVmean (+20 %; p = 0.001) were observed. Significant increases relative to peak axitinib concentration were observed at day 2 withdrawal for SUVmax and SUVmean, with no further significant increase from day 2 to day 7 of withdrawal. No significant change in SUVmax or SUVmean was observed during the treatment period, relative to baseline. VEGF concentration significantly increased when on drug (p < 0.001) and decreased back to a level indistinguishable from baseline by day 7 of drug washout (p = 0.448). No correlation between change in VEGF and change in imaging metrics was observed.
A significant increase in tumor proliferation was observed during withdrawal of axitinib therapy, and this flare occurred within 2 days of axitinib withdrawal. An exploratory analysis indicated that this flare may be associated with poor clinical outcome.
Cancer Chemotherapy and Pharmacology 05/2015; 76(1). DOI:10.1007/s00280-015-2779-7 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare complex quantitative magnetic resonance imaging (MRI) with MR spectroscopy (MRS) for quantification of hepatic steatosis (HS) and determine clinically significant MRI-based thresholds of HS in female youths.
This prospective, cross-sectional study was conducted in 132 healthy females (11-22 years, mean 13.3 ± 2). Proton density fat-fraction (PDFF) was measured using complex quantitative MRI and MRS. Body mass index (BMI), fasting labs [glucose, insulin, alanine aminotransferase (ALT), and other metabolic markers] were obtained. Outcomes were measured using regression analysis, Spearman-rank correlation, and receiver operator characteristics (ROC) analysis. HS was defined as MRI-PDFF >5.6 %.
HS was detected by MRI-PDFF in 15 % of all subjects. Linear regression demonstrated excellent correlation and agreement [r(2) = 0.96, slope = 0.97 (95 %CI: 0.94-1.00), intercept = 0.78 % (95 %CI: 0.58-0.98 %)] between MRI-PDFF and MRS-PDFF. MRI-PDFF had a sensitivity of 100 % (95 %CI: 0.79-1.00), specificity of 96.6 % (95 %CI: 0.91-0.99), and a kappa index of 87 % (95 %CI: 0.75-0.99) for identifying HS. In overweight subjects with HS, MRI-PDFF correlated with ALT (r = 0.84, p < 0.0001) and insulin (r = 0.833, p < 0.001), but not with BMI or WC. ROC analysis ascertained an optimal MRI-PDFF threshold of 3.5 % for predicting metabolic syndrome (sensitivity = 76 %, specificity = 83 %).
Complex quantitative MRI demonstrates strong correlation and agreement with MRS to quantify hepatic triglyceride content in adolescent girls and young women. A low PDFF threshold is predictive of metabolic syndrome in this population.
• Confounder-corrected quantitative MRI (ccqMRI) effectively measures hepatic triglyceride content in adolescent girls. • MRS and ccqMRI strongly correlate in liver proton density fat-fraction (PDFF) detection. • A PDFF threshold of 3.5 % may be predictive of paediatric metabolic syndrome.
European Radiology 04/2015; 25(10). DOI:10.1007/s00330-015-3724-1 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although fitness and obesity have been shown to be independent predictors of cardiometabolic disease risk in obese children, this interaction is not well defined in non-obese children. The purpose of this study was to define the relationships between peak aerobic capacity, body composition, and fasting insulin levels in non-obese middle school children.
148 middle school children (mean age 11.0 ± 2.1 years, 49% male) underwent determination of BMI z-score (BMIz), fasting glucose, fasting insulin (FI), body composition by DXA scan [lean body mass (LBM) and body fat percentage (BF%)], and peak oxygen uptake per kg of LBM (VO2peak). Univariate correlations and multivariate regression analysis were used to identify independent predictors of FI using age, sex, BF%, BMIz, and VO2peak.
FI was significantly related to VO2peak (r=-0.37, p<0.001), BF% (r=0.27, p<0.001), and BMIz (r=0.33, p=0.002). After inclusion in the multivariate model, VO2peak (p=0.018) and BMIz (p=0.043) remained significant predictors of FI, while age (p=0.39), sex (p=0.49), and BF% (p=0.72) did not.
Among non-obese middle school children, FI is independently related to aerobic fitness after accounting for age, sex, and body composition. Public health efforts to reduce cardiometabolic disease risk among all adolescents should include exercise programs to increase cardiovascular fitness.
[Show abstract][Hide abstract] ABSTRACT: Vaccination coverage rates can be improved through the application of complete and accurate immunization information systems (IISs).
Evaluate the completeness and accuracy of Wisconsin's IIS, the Wisconsin Immunization Registry (WIR).
Cross-sectional evaluation, comparing vaccination medical records (MRs) from provider clinics with WIR records.
Medical records of patients born during 2009 were randomly selected from 251 Wisconsin clinics associated with the Vaccines for Children Program.
Completeness: percentage of patients with client records in the WIR, percentage of patients up-to-date (%UTD) with the 4:3:1:3:3:1:4 vaccination series, and percentage of patients' MR vaccinations matched by administration date (±10 days) and type to vaccinations documented in the WIR. Accuracy: percentages of matched vaccinations with the same administration date, same trade name (TN), and same lot number.
Of the 1863 selected patient MRs, 98% (n = 1833) had WIR client records and 97% of their 30 899 vaccinations were documented in the WIR. The %UTD was 49.3% using the MR only, 76.5% using the WIR only, and 75.2% as estimated by the National Immunization Survey. Among matched vaccinations, 99% had the same administration date, 96% had the same TN, and 95% had the same lot number. Compared with patients from clinics that entered data into the WIR using data exchange from electronic health records, patients from clinics that entered data using the Web-based user interface were less likely to have client records in the WIR (odds ratio: 0.3; 95% confidence interval: 0.1-0.9) and less likely to have accurate TNs (odds ratio: 0.3; 95% confidence interval: 0.1-0.5).
The WIR was complete and accurate among this sample of children born during 2009 and provided a vaccination coverage assessment similar to the National Immunization Survey. Our results provide support for the expectation that meaningful use and other initiatives that increase data exchange from electronic health records to IISs will improve IIS data quality.
Journal of public health management and practice: JPHMP 01/2015; 21(3). DOI:10.1097/PHH.0000000000000216 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Urban environments can increase risk for development of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM) by limiting physical activity. This study examined, in a cohort of urban Hispanic youth, the relationship between daily physical activity (PA) measured by GPS, insulin resistance and cardiovascular fitness.
Hispanic middle school children (n = 141) were assessed for body mass index (BMI), IR (homeostasis model [HOMA-IR]), cardiovascular fitness (progressive aerobic cardiovascular endurance run [PACER]). PA was measured (GPS-PA) and energy expenditure estimated (GPS-EE) utilizing a global positioning mapping device worn for up to 7 days.
Students (mean age 12.7 ± 1.2 years, 52% female) spent 98% of waking time in sedentary activities, 1.7% in moderate intensity PA, and 0.3% in vigorous intensity. GPS analysis revealed extremely low amounts of physical movement during waking hours. The degree of low PA confounded correlation analysis with PACER or HOMA-IR.
Levels of moderate and vigorous intensity PA, measured by GPS, were extremely low in these urban Hispanic youth, possibly contributing to high rates of obesity and IR. Physical movement patterns suggest barriers to PA in play options near home, transportation to school, and in school recess time. GPS technology can objectively and accurately evaluate initiatives designed to reduce obesity and its morbidities by increasing PA.
International Journal of Pediatric Endocrinology 12/2014; 2014(1):25. DOI:10.1186/1687-9856-2014-25
[Show abstract][Hide abstract] ABSTRACT: Background:
RO4929097 is an oral inhibitor of γ -secretase that results in Notch signaling inhibition. Prior work has demonstrated that Notch signaling inhibition enhances chemotherapy sensitivity of cancer cells. This phase I study was conducted to determine maximum tolerated dose (MTD), toxicities and efficacy of RO4929097 and capecitabine in advanced solid tumors.
Patients with refractory solid tumors received capecitabine at a fixed dose of 1,000 mg/m(2) twice daily with escalating doses of RO4929097 on a 21-day cycle in a 3 + 3 design. Capecitabine was administered for 14 days and the RO49029097 once daily, 3 days per week, both for a 21 day cycle.
Thirty patients were treated on six dose levels (20 to 150 mg). The maximally tolerated dose was not reached. One dose limiting toxicity was observed at each level 3 through 6 (hypophosphatemia, fatigue, and nausea/vomiting). Three confirmed partial responses were observed: two patients with fluoropyrimide-refractory colon cancer and one patient with cervical cancer. Autoinduction of RO4929097 was demonstrated with increasing dose levels and duration.
The recommended phase 2 dose is capecitabine 1,000 mg/m(2) orally twice daily on days 1 through 14 with RO4929097 20 mg orally once daily on days 1-3, 8-10 and 15-17 with a 21 day cycle. Clinical benefit was observed in cervical and colon cancer. Autoinduction of RO4929097 was seen both with increasing cycle number and increasing dose. Plasma concentrations of RO4929097 were above those needed for Notch inhibition.
Investigational New Drugs 10/2014; 33(1). DOI:10.1007/s10637-014-0166-6 · 2.92 Impact Factor