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Combination Approach (combination + approach)
Selected AbstractsAchieving Goal Blood Pressure in Patients With Type 2 Diabetes: Conventional Versus Fixed-Dose Combination ApproachesJOURNAL OF CLINICAL HYPERTENSION, Issue 3 2003George L. Bakris MD Data from the Third National Health and Nutrition Examination Survey (NHANES III) demonstrate that only 11% of people with diabetes who are treated for high blood pressure achieve the blood pressure goal of <130/85 mm Hg recommended in the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The current study tests the hypothesis that initial therapy with a fixed-dose combination will achieve the recommended blood pressure goal in patients with type 2 diabetes faster than conventional monotherapy. This randomized, double-blind, placebo-controlled study had as a primary end point achievement of blood pressure <130/85 mm Hg. Participants (N=214) with hypertension and type 2 diabetes received either amlodipine/benazepril 5/10 mg (combination) or enalapril 10 mg (conventional) once daily for 4 weeks, titrated to 5/20 mg/day or 20 mg/day, respectively at this time, if target blood pressure was not achieved. Hydrochlorothiazide (HCTZ) 12.5 mg/day was added for the final 4 weeks, if target blood pressure was still not reached. Time from baseline to achieve blood pressure <130/85 mm Hg was shorter in the combination group (5.3±3.1 weeks combination vs. 6.4±3.8 weeks conventional; p=0.001). At 3 months, more participants in the combination group achieved treatment goal (63% combination vs. 37% conventional; p=0.002). Data analysis at 3 months comparing blood pressure control rates between the fixed-dose combination group (with out HCTZ) to the conventional group (receiving HCTZ) showed an even greater disparity in blood pressure goal achievement (87% combination without HCTZ vs. 37% conventional group with HCTZ; p=0.0001). We conclude that initial therapy with a fixed-dose combination may be more efficacious than conventional monotherapy approaches for achieving blood pressure goals in the diabetic patient. A fixed-dose combination approach appears as safe as the current conventional approaches. [source] Supported Chiral Monodentate Ligands in Rhodium-Catalysed Asymmetric Hydrogenation and Palladium-Catalysed Asymmetric Allylic AlkylationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2009Bert H. G. Swennenhuis Abstract A family of monodentate polystyrene-supported phosphites, phosphoramidites and phosphanes has been prepared and evaluated as ligands in rhodium-catalysed asymmetric hydrogenation and palladium-catalysed asymmetric allylic alkylation. The supported ligands yielded active and enantioselective catalysts, which in selected cases match the performance of the nonsupported counterparts. As expected, the performance of the supported ligands in the rhodium-catalysed hydrogenation depends on the nature of the ligand, the type of polymeric support, as well as on the substrate. Additionally, the supported ligands have been applied in the monodentate ligand combination approach, by combining them with nonsupported monodentate ligands. The partially supported heteroligand combinations possess different catalytic properties than the related nonsupported combinations. The heteroligand species, however, are not formed selectively, and nonsupported homoleptic complexes also contribute to the overall activity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Achieving Goal Blood Pressure in Patients With Type 2 Diabetes: Conventional Versus Fixed-Dose Combination ApproachesJOURNAL OF CLINICAL HYPERTENSION, Issue 3 2003George L. Bakris MD Data from the Third National Health and Nutrition Examination Survey (NHANES III) demonstrate that only 11% of people with diabetes who are treated for high blood pressure achieve the blood pressure goal of <130/85 mm Hg recommended in the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The current study tests the hypothesis that initial therapy with a fixed-dose combination will achieve the recommended blood pressure goal in patients with type 2 diabetes faster than conventional monotherapy. This randomized, double-blind, placebo-controlled study had as a primary end point achievement of blood pressure <130/85 mm Hg. Participants (N=214) with hypertension and type 2 diabetes received either amlodipine/benazepril 5/10 mg (combination) or enalapril 10 mg (conventional) once daily for 4 weeks, titrated to 5/20 mg/day or 20 mg/day, respectively at this time, if target blood pressure was not achieved. Hydrochlorothiazide (HCTZ) 12.5 mg/day was added for the final 4 weeks, if target blood pressure was still not reached. Time from baseline to achieve blood pressure <130/85 mm Hg was shorter in the combination group (5.3±3.1 weeks combination vs. 6.4±3.8 weeks conventional; p=0.001). At 3 months, more participants in the combination group achieved treatment goal (63% combination vs. 37% conventional; p=0.002). Data analysis at 3 months comparing blood pressure control rates between the fixed-dose combination group (with out HCTZ) to the conventional group (receiving HCTZ) showed an even greater disparity in blood pressure goal achievement (87% combination without HCTZ vs. 37% conventional group with HCTZ; p=0.0001). We conclude that initial therapy with a fixed-dose combination may be more efficacious than conventional monotherapy approaches for achieving blood pressure goals in the diabetic patient. A fixed-dose combination approach appears as safe as the current conventional approaches. [source] Choosing among competing econometric forecasts: Regression-based forecast combination using model selectionJOURNAL OF FORECASTING, Issue 6 2001Norman R. Swanson Abstract Forecast combination based on a model selection approach is discussed and evaluated. In addition, a combination approach based on ex ante predictive ability is outlined. The model selection approach which we examine is based on the use of Schwarz (SIC) or the Akaike (AIC) Information Criteria. Monte Carlo experiments based on combination forecasts constructed using possibly (misspecified) models suggest that the SIC offers a potentially useful combination approach, and that further investigation is warranted. For example, combination forecasts from a simple averaging approach MSE-dominate SIC combination forecasts less than 25% of the time in most cases, while other ,standard' combination approaches fare even worse. Alternative combination approaches are also compared by conducting forecasting experiments using nine US macroeconomic variables. In particular, artificial neural networks (ANN), linear models, and professional forecasts are used to form real-time forecasts of the variables, and it is shown via a series of experiments that SIC, t -statistic, and averaging combination approaches dominate various other combination approaches. An additional finding is that while ANN models may not MSE-dominate simpler linear models, combinations of forecasts from these two models outperform either individual forecast, for a subset of the economic variables examined. Copyright © 2001 John Wiley & Sons, Ltd. [source] Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin GJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. L. Craigmill Investigators frequently face the quandary of how to interpret the oftentimes disparate pharmacokinetic parameter values reported in the literature. Combining of data from multiple studies (meta-analysis) is a useful tool in pharmacokinetics. Few studies have explored the use of meta-analysis for veterinary species. Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta-analysis. Therefore, in this study we performed a meta-analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle. The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points). Three methods were used to calculate the parameters. The first was a simple statistical analysis of the parameter values reported in each paper. The second method was a standard Two-Stage Method (TSM) using the mean concentration vs. time data extracted from each paper. The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs. time data reported in the various papers, treating the mean data as if each set came from an individual animal. The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG. The only significant difference noted was for OTC absorption half-lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation. The NMEM procedure offers the possibility of including covariates such as dose, age, and weight. In this study the covariates did not influence the derived parameters. A combination approach to meta-analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach. [source] Combination of multidimensional navigator echoes data from multielement RF coilMAGNETIC RESONANCE IN MEDICINE, Issue 4 2010Junmin Liu Abstract Until now, only one-dimensional navigator-echo techniques have been implemented with multielement RF coils. For the multidimensional navigator echoes, which extract six-degree of freedom motion information from the raw k-space data, an efficient raw data combination approach is needed. In this work, three combination approaches, including summation of the complex raw data, summation following phase alignment, and summation of the squares of the k-space magnitude profiles, were evaluated with the spherical navigator echoes (SNAV) technique. In vivo brain imaging experiments were used to quantify accuracy and precision and demonstrated that SNAVs acquired with an eight-channel head coil can determine the rotation and translation in range up to 10° and 20 mm with subdegree and submillimeter accuracy, respectively. Results from a 3D brain volume realignment experiment showed excellent agreement between baseline images and SNAV-aligned follow-up volumes. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [source] Enhancement of Ad-p53 Therapy with Docetaxel in Head and Neck Cancer,THE LARYNGOSCOPE, Issue 11 2004George H. Yoo MD Abstract Objective: The objective of this project was to determine the mechanisms in which docetaxel enhances Ad-p53 tumor suppressive effects in head and neck cancer. Background: In advanced head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate is less than 40%. Because patients with advanced HNSCC have a high rate of local-regional failure (40-60%) with existing treatment modalities, aggressive local therapy approaches need to be developed. Previous data show that docetaxel or Ad-p53 alone have significant anti-tumor activity in HNSCC. Before testing whether a combination approach (Ad-p53 and docetaxel) could be developed in clinical trials, preclinical experiments were performed. Methods: The p53 gene was overexpressed in 2 head and neck squamous carcinoma (HNSCC) cell lines, HN30 and HN12, and a murine Balb/c mucoepidermoid carcinoma (BMEC) cell line. Docetaxel's enhancement of adenoviral transduction (bGAL expression), coxsakie-adenovirus receptor (CAR) expression, and Ad-p53 induction of apoptosis (Annexin V expression) were measured. The modulation of regulators in the cell cycle, apoptosis and signal transduction pathways were measured using Western blot. Results: Docetaxel increased adenoviral transduction, which was dependent on the dose of docetaxel and levels of Ad-bGAL. The enhanced viral transduction was due in part to the upregulation of the CAR protein. Pretreatment with docetaxel enhanced Ad-p53-induced apoptosis through increased expression of exogenous p53. Together, the combination of docetaxel and Ad-p53 altered expression of key regulators in the cell cycle, apoptosis and signal transduction pathways with an increase in the expression of p53, bax, cleaved PARP, cleaved caspase-3 and phosphorylation of c-Jun at position at 63Ser. Cyclin A and B1 expression were down regulated by docetaxel and Ad-p53. When comparing the docetaxel-resistant to sensitive cell lines, the altered expression of p27 and skp1 by docetaxel and Ad-p53 were dissimilar between these cell lines. Conclusions: Docetaxel enhanced Ad-p53 transduction and increased expression of exogenous p53 gene transfer, apoptosis, and antitumor mechanisms. These results support a clinical combination of docetaxel with p53 gene therapy in patients with head and neck cancer. [source] Low recurrence rate after surgery for dermatofibrosarcoma protuberansCANCER, Issue 5 2004A multidisciplinary approach from a single institution Abstract BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma with a propensity for local recurrence. Treatments with wide excision, Mohs surgery, and other approaches have been reported with widely variable local control rates. The objective of this study was to review the experience with a multidisciplinary approach employing wide excision and Mohs surgery selectively in the treatment of patients with DFSP at a single academic institution over the past 10 years. METHODS The records of 62 patients with 63 DFSP tumors who underwent wide excision, Mohs surgery, or a multidisciplinary combination approach from January 1991 to December 2000 were reviewed retrospectively. Primary endpoints included the ability to extirpate the DFSP lesion completely, the tumor recurrence rate, and the need for skin grafts or local tissue flaps. Additional objectives included defining surgical practice patterns at the authors' institution. RESULTS Sixty-three DFSP lesions were removed from 62 patients. At a median follow-up of 4.4 years, no local or distant recurrences were detected in any patient. Forty-three lesions were treated with wide local excision, 11 lesions were treated with Mohs surgery, and 9 lesions were treated with a combination approach. Ninety-five percent of lesions that were approached initially with wide local excision were cleared histologically. Two patients (5%) received postoperative radiation for positive margins after undergoing maximal excision. Eighty-five percent of lesions that were approached initially with Mohs surgery were cleared histologically. The remaining 15% of lesions subsequently were cleared surgically with a wide excision. DFSP lesions that were approached initially with Mohs surgery tended to be smaller. Patients with head and neck lesions most often underwent Mohs surgery or were treated with a multidisciplinary combination approach (87%). CONCLUSIONS Wide local excision with careful pathologic analysis of margins was found to have a very low recurrence rate and was used for the majority of patients with DFSP lesions at the authors' institution. Wide local excision, Mohs surgery, and a multidisciplinary combination approach, selected based on both tumor and patient factors, were capable of achieving very high local control rates in the treatment of DFSP. The evolution of a multidisciplinary approach has provided a level of expertise that no single individual could achieve for the treatment of the full spectrum of DFSP lesions at the authors' institution. Cancer 2004;100:1008,16. © 2004 American Cancer Society. [source] The patient with cardiovascular disease: Treatment strategies for preventing major eventsCLINICAL CARDIOLOGY, Issue S2 2006Michael Cuffe M.D. Abstract An abundance of clinical data exists to support the ability of pharmacologic interventions to reduce risk for vascular events significantly; however, there remains a gap between this evidence and current clinical practice. Recent data from large-scale, placebo-controlled statin trials demonstrate that these agents dramatically reduce risk for cardiovascular events, even in moderate-risk patients with normal to moderately elevated cholesterol levels. Data from trials of a broad range of antihypertensives reinforce the value of blood pressure (BP) management and indicate that some of these agents may have additional benefits beyond BP reduction. Similarly, meta-analyses of randomized trials confirm that antiplatelet therapy prevents serious cardiovascular events in a wide range of high-risk patients. Each of these interventions alone has been demonstrated to reduce the risk for vascular events by approximately 25 to 30%. A combination approach utilizing intensive risk-reducing therapy with more than one of these agents has the potential to reduce the risk for vascular events by as much as 75%. Combined with nonpharmacologic risk reduction strategies, including exercise, diet, and smoking cessation, an opportunity exists to reduce the incidence of both first and recurrent cardiovascular events dramatically. [source] Choosing among competing econometric forecasts: Regression-based forecast combination using model selectionJOURNAL OF FORECASTING, Issue 6 2001Norman R. Swanson Abstract Forecast combination based on a model selection approach is discussed and evaluated. In addition, a combination approach based on ex ante predictive ability is outlined. The model selection approach which we examine is based on the use of Schwarz (SIC) or the Akaike (AIC) Information Criteria. Monte Carlo experiments based on combination forecasts constructed using possibly (misspecified) models suggest that the SIC offers a potentially useful combination approach, and that further investigation is warranted. For example, combination forecasts from a simple averaging approach MSE-dominate SIC combination forecasts less than 25% of the time in most cases, while other ,standard' combination approaches fare even worse. Alternative combination approaches are also compared by conducting forecasting experiments using nine US macroeconomic variables. In particular, artificial neural networks (ANN), linear models, and professional forecasts are used to form real-time forecasts of the variables, and it is shown via a series of experiments that SIC, t -statistic, and averaging combination approaches dominate various other combination approaches. An additional finding is that while ANN models may not MSE-dominate simpler linear models, combinations of forecasts from these two models outperform either individual forecast, for a subset of the economic variables examined. Copyright © 2001 John Wiley & Sons, Ltd. [source] Combination of multidimensional navigator echoes data from multielement RF coilMAGNETIC RESONANCE IN MEDICINE, Issue 4 2010Junmin Liu Abstract Until now, only one-dimensional navigator-echo techniques have been implemented with multielement RF coils. For the multidimensional navigator echoes, which extract six-degree of freedom motion information from the raw k-space data, an efficient raw data combination approach is needed. In this work, three combination approaches, including summation of the complex raw data, summation following phase alignment, and summation of the squares of the k-space magnitude profiles, were evaluated with the spherical navigator echoes (SNAV) technique. In vivo brain imaging experiments were used to quantify accuracy and precision and demonstrated that SNAVs acquired with an eight-channel head coil can determine the rotation and translation in range up to 10° and 20 mm with subdegree and submillimeter accuracy, respectively. Results from a 3D brain volume realignment experiment showed excellent agreement between baseline images and SNAV-aligned follow-up volumes. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [source] | ||||||||||