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Stanton A.V.,Royal College of Surgeons in Ireland | Gradman A.H.,Western Pennsylvania Hospital | Schmieder R.E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Nussberger J.,University of Lausanne | And 2 more authors.
Hypertension | Year: 2010

Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo-and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after ≥4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (>10 mm Hg; P=0.30) or diastolic (>5 mm Hg; P=0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%; P<0.001). None of the 536 patients with plasma renin activity data who received 300 mg of aliskiren exhibited an increase in systolic pressure >10 mm Hg that was associated with an increase in plasma renin activity >0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure. © 2010 American Heart Association, Inc. Source


Rowland M.R.,University of Pittsburgh | Lesnock J.L.,Mid Atlantic Gynecologic Oncology of Mon General Hospital | Farris C.,RAND Corporation | Kelley J.L.,University of Pittsburgh | Krivak T.C.,Western Pennsylvania Hospital
American Journal of Obstetrics and Gynecology | Year: 2015

Objective Treatment for advanced-stage epithelial ovarian cancer (AEOC) includes primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). A randomized controlled trial comparing these treatments resulted in comparable overall survival (OS). Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS. We sought to evaluate the cost implications of NACT relative to PDS in AEOC patients 65 years old or older. Study Design A 5 year Markov model was created. Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel (CT). Arm 2 modeled 3 cycles of CT, followed by interval debulking surgery and then 3 additional cycles of CT. Parameters included OS, surgical complications, probability of treatment initiation, treatment cost, and quality of life (QOL). OS was assumed to be equal based on the findings of the international randomized control trial. Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates. Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates. Sensitivity analyses were performed. Results Assuming equal survival, NACT produces a cost savings of $5616. If PDS improved median OS by 1.5 months or longer, PDS would be cost effective (CE) at a $100,000/quality-adjusted life-year threshold. If PDS improved OS by 3.2 months or longer, it would be CE at a $50,000 threshold. The model was robust to variation in costs and complication rates. Moderate decreases in the QOL with NACT would result in PDS being CE. Conclusion A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older. Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $100,000/quality-adjusted life-year threshold. Our results support further evaluation of the effects of PDS on OS, QOL and complications in AEOC patients 65 years old or older. © 2015 Elsevier Inc. All rights reserved. Source


Gill B.S.,University of Pittsburgh | Lin J.F.,University of Pittsburgh | Krivak T.C.,Western Pennsylvania Hospital | Sukumvanich P.,University of Pittsburgh | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities.Methods and Materials Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival.Results A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61′ 95% confidence interval, 1.27-2.04′ P<.01).Conclusions Consolidation brachytherapy is a critical treatment component for locally advanced cervical cancer; however, there has been declining utilization of brachytherapy. Increased use of IMRT and SBRT boost coupled with increased mortality risk should raise concerns about utilizing these approaches over brachytherapy. © 2014 Elsevier Inc. Source


Kirkham B.W.,Guys and St Thomas NHS Foundation Trust | Wasko M.C.,Temple University | Hsia E.C.,Janssen Research and Development LLC | Hsia E.C.,University of Pennsylvania | And 7 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD). Methods Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg +placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections ( placebo and golimumab) were given every 4 weeks. Patients with an insufficient response entered early escape at week 16 (GO-FORWARD) or 28 (GO-BEFORE). All placebo+MTX patients in GO-FORWARD crossed over to golimumab 50 mg+MTX at week 24. Changes from baseline to weeks 14 (GO-FORWARD) or 24 (GO-BEFORE), and 52 in serum lipid levels and inflammatory markers were assessed. Results At week 14 in the GO-FORWARD trial, total cholesterol (TC), high-density lipoprotein (HDL) and lowdensity lipoprotein (LDL) increased in golimumab+MTX patients versus MTX-only patients (16.00 vs 2.00 (p<0.001); 3.00 vs 0.00 ( p<0.05); 8.00 vs 4.00 (p<0.001); respectively); favourable changes in LDL subfractions were only observed in golimumab-treated patients. At week 24 in GO-BEFORE, TC and LDL increased, and LDL subfractions improved in the MTX-only and golimumab+MTX groups. Inflammatory markers of CVD risk improved significantly with golimumab+MTX versus placebo+MTX in both studies and were generally maintained through week 52. Atherogenic indices were generally stable. Conclusions While TC and LDL levels increased mildly in RA patients receiving golimumab+MTX, atherogenic indices generally remained stable, favourable changes in LDL subfractions were observed, and inflammatory markers improved. Source


Costa R.B.,Western Pennsylvania Hospital | Kurra G.,Western Pennsylvania Hospital | Greenberg L.,Allegheny General Hospital | Geyer C.E.,Allegheny General Hospital
Annals of Oncology | Year: 2010

Background: Trastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline-containing regimens. Design: This paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04]. Results: The addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%-35%) in the large trials. In NSABP B-31/NCCTG N9831, 5.0%-6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline-containing trastuzumab arms (1.9%-3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%). Conclusions: Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

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