Jens C Eickhoff

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (179)638.71 Total impact

  • Clinical Infectious Diseases 06/2015; DOI:10.1093/cid/civ514 · 9.42 Impact Factor
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    ABSTRACT: 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. 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. 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. Sixty-five patients were evaluated prior to TPCC implementation (cohort 1). Seventy patients (cohort 2) were evaluated after initiation of TPCC and 68 patients (cohort 3) were evaluated following 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. 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. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
    Journal of pain and symptom management 06/2015; DOI:10.1016/j.jpainsymman.2015.04.022 · 2.74 Impact Factor
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    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; DOI:10.1007/s00280-015-2783-y · 2.57 Impact Factor
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    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.
    06/2015; DOI:10.1513/AnnalsATS.201410-470OC
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    ABSTRACT: Potential cytochrome P-450 (CYP) drug-drug interactions in adults with metastatic solid tumors and their effect on eligibility for Phase I clinical trials were characterized. This study included adult patients with metastatic solid tumors seen by a medical oncologist from January 2008 through July 2011. The medications used by these patients were identified. Each medication's potential for interacting with CYP isozymes was also characterized. Medication changes required to meet Phase I trial eligibility criteria were also reviewed. Data from 1773 patients were analyzed: 1489 were not enrolled in a Phase I trial and 284 were enrolled in a Phase I trial. Polypharmacy was significantly more prevalent in the group enrolled in a Phase I trial compared with those not enrolled (95% versus 80%, p < 0.001). The majority of patients not enrolled in a Phase I trial were taking at least one CYP isozyme inhibitor (87%) and at least one CYP isozyme inducer (45%). In a separate analysis, four Phase I trials were evaluated. Of 295 screened patients, 3.2% could not enroll due to concurrent medications. Charts from 74 enrolled patients revealed 655 concurrent medications-93 medications required further review for eligibility involving 51 (69%) of patients. Of the 93 medications, 38 (41%) were stopped and 41 (44%) were changed for the study. Polypharmacy and the use of medications that interact with CYP isoyzmes were common in adult patients with metastatic solid tumors. Patients enrolling in Phase I studies often require medication changes to meet eligibility requirements. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
    American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 06/2015; 72(11):958-65. DOI:10.2146/ajhp140591 · 2.21 Impact Factor
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    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; DOI:10.1007/s00280-015-2779-7 · 2.57 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P5-19-20-P5-19-20. DOI:10.1158/1538-7445.SABCS14-P5-19-20 · 9.28 Impact Factor
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    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; DOI:10.1007/s00330-015-3724-1 · 4.34 Impact Factor
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    ABSTRACT: Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N(1) -acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine-rich PCa cells. We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs. Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early-stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease. Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed-forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate-resistant prostate cancer growth. Prostate 9999: XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    The Prostate 04/2015; 75(11). DOI:10.1002/pros.22996 · 3.57 Impact Factor
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    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.
    Pediatric exercise science 04/2015; 27(2). DOI:10.1123/pes.2014-0098 · 1.61 Impact Factor
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    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; DOI:10.1097/PHH.0000000000000216 · 1.47 Impact Factor
  • M Bruce Edmonson · Jens C Eickhoff · Chong Zhang
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    ABSTRACT: To describe the clinical spectrum and frequency of acute care revisits after tonsillectomy in a population-based sample from a single state in the US. We used California state discharge databases from 2009 to 2011 to retrospectively identify retrospectively routine tonsillectomy discharges in residents <25 years of age and to establish record linkage to revisits within 30 days at ambulatory surgery, inpatient, and emergency department facilities statewide. Percentages and descriptive statistics were sample-weighted, and revisit rates were adjusted for demographic factors, expected payer, chronic conditions, surgical indication, facility type, and clustering. Records were available for 35 085 index tonsillectomies, most of which were performed at hospital-owned ambulatory and inpatient facilities. There were 4944 associated revisits: 3761 (75.9%) treat-and-release emergency room visits, 816 (17.1%) inpatient admissions, and 367 (7.0%) ambulatory surgery visits. Most revisits (3225 [67.7%]) were unrelated to bleeding; these typically occurred early (mode, day 2) and were commonly associated with diagnosis codes indicating pain, nausea/vomiting, or dehydration. Crude all-cause revisit and readmission rates were 10.5% and 2.1%, respectively. Adjusted all-cause revisit rates (range, 8.6%-24.5%) were lowest in young children, increased in adolescents, and peaked in young adults. Adjusted bleeding-related revisit rates increased abruptly in adolescents and reached 13.9% in males (6.8% in females, P < .001) ages 20-24 years. Acute care revisits after tonsillectomy performed at predominately hospital-owned facilities in California are common and strongly age-related. Most revisits are early treat-and-release outpatient encounters, and these are usually associated with potentially preventable problems such as pain, nausea and vomiting, and dehydration. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Pediatrics 12/2014; 166(3). DOI:10.1016/j.jpeds.2014.11.009 · 3.74 Impact Factor
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    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
  • Shannon M. Dean · Jens C. Eickhoff · Leigh Anne Bakel
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    ABSTRACT: Providers nationally have observed a decline in the quality of documentation after implementing electronic health records (EHRs). In this pilot study, we examined the effectiveness of an intervention bundle designed to improve resident progress notes written in an EHR and to establish the reliability of an audit tool used to evaluate notes. The bundle consisted of establishing note-writing guidelines, developing an aligned note template, and educating interns about the guidelines and using the template. Twenty-five progress notes written by pediatric interns before and after this intervention were examined using an audit tool. Reliability of the tool was evaluated using the intraclass correlation coefficient (ICC). The total score of the audit tool was summarized in terms of means and standard deviation. Individual item responses were summarized using percentages and compared between the pre- and postintervention assessment using the Fisher exact test. The ICC for the audit tool was 0.96 (95% confidence interval: 0.91–0.98). A significant improvement in the total note score and in questions related to note clutter was seen. No significant improvement was seen for questions related to copy-paste. The study suggests that an intervention bundle can lead to some improvements in note writing. Journal of Hospital Medicine 2014. © 2014 Society of Hospital Medicine
    Journal of Hospital Medicine 11/2014; 10(2). DOI:10.1002/jhm.2283 · 2.08 Impact Factor
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    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. Methods 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. Results 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. Conclusions 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 · 2.93 Impact Factor
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    ABSTRACT: Purpose Retreatment with bortezomib (B) is often considered for patients with relapsed multiple myeloma (MM), but this strategy is hindered by uncertainty of response and emergence of B-induced peripheral neuropathy (PN). We incorporated acetyl-l-carnitine (ALCAR) to prevent PN and allow for adequate dosing. We also investigated the correlation between B-inducible NF-κB activation and response to therapy. Methods Nineteen patients with relapsed/refractory MM received up to 8 cycles of intravenous bortezomib, doxorubicin and oral low-dose dexamethasone (BDD) to evaluate response and toxicity. Thirteen additional patients received prophylactic ALCAR (BDD-A). Patients receiving BDD-A were evaluated by FACT-GOG-TX, FACIT-Fatigue, Neuropathic Pain index (NPI) and Grooved Pegboard (GP) testing. Primary MM cells from 11 patients were tested for B-inducible NF-κB activation. Results Seventy-six percent of subjects were refractory to previous treatment, 39 % refractory to bortezomib. Median cycles received were 5. CR + PR for the entire group were 53 % and did not differ between groups. Incidence of ≥3 PN was 32 % in the BDD group versus 15 % in the BDD-A group (p = ns). Patient-reported fatigue and PN measured by FACT-GOG-TX increased throughout the treatment period in the BDD-A group, although time to complete GP testing declined. In a sub-study examining constitutive bortezomib-inducible NF-κB activity in primary subject-specific MM cells, the presence of NF-κB activation correlated with lower likelihood of response. Conclusions Addition of ALCAR to BDD did not alter the incidence or severity of PN in relapsed MM patients receiving a B-based regimen. Bortezomib-inducible NF-κB activation in patient-derived primary MM cells may be associated with poorer response.
    Cancer Chemotherapy and Pharmacology 08/2014; 74(4). DOI:10.1007/s00280-014-2550-5 · 2.57 Impact Factor
  • The Journal of Infectious Diseases 08/2014; 211(3). DOI:10.1093/infdis/jiu478 · 5.78 Impact Factor
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    ABSTRACT: Yttrium 90-ibritumomab tiuxetan (90Y-IT) radioimmunotherapy has proved to be effective in relapsed follicular lymphoma (FL). We conducted a clinical trial in which 90Y-IT followed by maintenance rituximab (MR) was evaluated as initial therapy for high-tumor-burden FL.
    Clinical advances in hematology & oncology: H&O 08/2014; 12(8):509-15.
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    ABSTRACT: Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction and failure. Paradoxically, women are more frequently diagnosed with PAH but have better RV systolic function and survival rates than men. The mechanisms by which sex differences alter PAH outcomes remain unknown. Here, we sought to study the role of estrogen in RV functional remodeling in response to PAH. The SU5416-Hypoxia (SuHx) mouse model of PAH was used. To study the role of estrogen, female mice were ovariectomized and then treated with estrogen or placebo. SuHx significantly increased RV afterload and resulted in RV hypertrophy. Estrogen treatment attenuated the increase in RV afterload compared to the untreated group (effective arterial elastance: 2.3±0.1 mmHg/µl vs. 3.2±0.3 mmHg/µl and this was linked to preserved pulmonary arterial compliance (compliance: 0.013±0.001 mm<2/sup>/mmHg vs. 0.010±0.001 mm<2/sub>/mmHg, P<0.05) and decreased distal muscularization. Despite lower RV afterload in the estrogen-treated SuHx group, RV contractility increased to a similar level as the placebo-treated SuHx group, suggesting an inotropic effect of estrogen on RV myocardium. Consequently, compared to the placebo-treated SuHx group, estrogen improved RV ejection fraction and cardiac output (EF: 57±2% vs. 44 ± 2% and CO: 9.7±0.4 ml/min vs. 7.6±0.6 ml/min; P<0.05). Our study demonstrates for the first time that estrogen protects RV function in the SuHx model of PAH in mice directly by stimulating RV contractility and indirectly by protecting against pulmonary vascular remodeling. These results underscore the therapeutic potential of estrogen in PAH.
    AJP Heart and Circulatory Physiology 06/2014; 307(3). DOI:10.1152/ajpheart.00758.2013 · 4.01 Impact Factor
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    ABSTRACT: Background. We estimated the vaccine effectiveness (VE) of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents during a statewide outbreak of pertussis in Wisconsin during 2012. Methods. We used the population-based Wisconsin Immunization Registry (WIR) to construct a cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination histories. Reports of laboratory-confirmed pertussis with onset during 2012 were matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE estimates [(1 - IRR)*100%], by year of Tdap vaccine receipt and brand (Boostrix/Adacel), were estimated using Poisson regression. Results. Tdap VE decreased with increasing time since receipt, with VEs of 75.3% (95% confidence interval [CI], 55.2%-86.5%) for receipt during 2012, 68.2% (95% CI, 60.9%-74.1%) for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and 11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates were higher among Boostrix recipients than among Adacel recipients. Among Tdap recipients, increasing time since receipt was associated with increased risk, and receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis (adjusted IRR, 0.62 [95% CI, .52-.74]). Conclusions. Our results demonstrate waning immunity following vaccination with either Tdap brand. Boostrix was more effective than Adacel in preventing pertussis in our cohort, but these findings may not be generalizable to adolescent cohorts that received different diphtheria-tetanus-acellular pertussis vaccines (DTaP) during childhood and should be further examined in studies that include childhood DTaP history.
    The Journal of Infectious Diseases 06/2014; 210(6). DOI:10.1093/infdis/jiu322 · 5.78 Impact Factor

Publication Stats

3k Citations
638.71 Total Impact Points

Institutions

  • 2003–2015
    • University of Wisconsin–Madison
      • • Department of Biostatistics and Medical Informatics
      • • Department of Medicine
      Madison, Wisconsin, United States
  • 2014
    • Medical College of Wisconsin
      Milwaukee, Wisconsin, United States
  • 2009–2013
    • Colorado State University
      • • College of Veterinary Medicine and Biomedical Sciences
      • • Department of Clinical Sciences
      • • Department of Statistics
      Fort Collins, Colorado, United States
  • 2008–2011
    • University of Wisconsin - Stout
      Menominee, Wisconsin, United States
  • 2010
    • The American Board of Family Medicine
      Lexington, Kentucky, United States
    • The Children's Hospital of Philadelphia
      Filadelfia, Pennsylvania, United States
  • 2007
    • Klinikum Ludwigshafen
      Ludwigshafen, Rheinland-Pfalz, Germany