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Dual Therapy (dual + therapy)
Selected AbstractsCombination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 6 2005Suzanne M. Strowig The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [source] Combined Ketogenic Diet and Vagus Nerve Stimulation: Rational Polytherapy?EPILEPSIA, Issue 1 2007Eric H. Kossoff Summary:,Objective: The concept of "rational polypharmacy" has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies. Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy. Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4,24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5,96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness. Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use. [source] Increased rate of prematurity associated with antenatal antiretroviral therapy in a German/Austrian cohort of HIV-1-infected womenHIV MEDICINE, Issue 1 2008I Grosch-Woerner Objective The aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women. Methods Prospective monitoring of 183 mother,child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German,Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as <36 weeks' gestation for these analyses. Results Of 183 mother,child pairs, 42% were exposed to antenatal monotherapy and 17% to dual therapy. Of the 75 women exposed to highly active antiretroviral therapy (HAART), 21 (28%) received protease inhibitor (PI)-based HAART and the remaining 54 received nonnucleoside reverse transcriptase inhibitor-based HAART. In multivariable analysis (176 pregnancies), PI-based HAART exposure during pregnancy was associated with an increased risk of premature delivery [adjusted odds ratio 3.40; 95% confidence interval (CI) 1.13,10.2; P=0.029, compared with monotherapy]. Congenital abnormalities affected 3.3% infants. Perinatally, 18.9% of children (34 of 179) had respiratory problems requiring interventions, which were associated with prematurity but not with type of treatment exposure. From adjusted regression analysis, the mean birth weight z -score for children exposed to HAART with PI (+0.46; 95% CI 0.01,0.92; P=0.047) or dual therapy (+0.43; 95% CI 0.03,0.82; P=0.034) was slightly but significantly higher than that for those exposed to monotherapy; head circumference was appropriate for gestational age and there were no significant differences between treatment groups. Conclusions Use of antenatal PI-based HAART initiated before or during pregnancy was associated with a significantly increased risk of premature delivery at <36 weeks' gestation. The overall crude prematurity rate was 34% (63 of 183; 95% CI 28,42). [source] Clinical features and predictors of survival of AIDS-related non-Hodgkin's lymphoma in a population-based case series in Sydney, AustraliaHIV MEDICINE, Issue 5 2004MC Robotin Objectives To analyse clinical features and predictors of survival for AIDS-related non-Hodgkin's lymphoma (NHL) in the era of highly active antiretroviral therapy (HAART), compared to earlier in the HIV epidemic. Methods All AIDS-NHL cases diagnosed at three inner Sydney hospitals caring for people with AIDS during 1985,2001 were identified through medical record searches. Demographic, clinical, immunological and histopathological information was recorded. Year of NHL diagnosis was grouped into three periods, corresponding to whether monotherapy (1985,1991), dual therapy (1992,1995) or HAART (1996,2001) was the main treatment for HIV infection. Statistical comparisons were made between the pre-HAART and post-HAART eras. Results Three hundred cases of AIDS-NHL were identified. Divergent trends were identified for systemic and primary central nervous system (CNS) NHL. For systemic NHL, the CD4 count at NHL diagnosis increased markedly to 208 cells/,L in the post-HAART era (P=0.014) and there was a trend towards presentation as the first AIDS-defining illness (69%, P=0.053), and as earlier stage NHL disease (42%, P=0.048). Median survival time increased from 4.2 months in 1985,1991 to 19 months in the post-HAART era (P<0.001). In a multivariate model, predictors of poor survival from systemic NHL included: NHL diagnosis after another AIDS-defining illness (P<0.001), stage 4 NHL (P<0.001), presentation at extra lymphatic sites (P=0.001), and nonreceipt of chemotherapy (P=0.002). After adjusting for the factors, those diagnosed in the era of HAART had a significant 56% reduction in rate of death (P<0.001). In contrast, for CNS NHL, clinical features were little changed and survival did not improve in the era of HAART. Conclusions Systemic NHL is presenting earlier in the course of HIV disease, and at a less advanced NHL stage. There has been a marked improvement in survival in the era of HAART even after adjustment for other prognostic variables. In contrast, primary CNS NHL remains a disease which presents late in the course of HIV infection and is associated with a very poor prognosis. [source] Comparison of efficacies of dual therapy and triple therapy using rabeprazole in second-line eradication of Helicobacter pylori in JapanALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2006T. KAWAI Summary Background The only authorized second-line Helicobacter pylori regimen in Japan is proton pump inhibitor + amoxycillin + clarithromycin. However, it has been reported that this second-line regimen is not effective. In this study, we evaluated the efficacy of dual and triple eradication therapies using rabeprazole as second-line H. pylori eradication regimens. Aim To evaluate the efficacy of dual and triple eradication therapies using rabeprazole as second-line H. pylori eradication therapy. Methods Sixty-two H. pylori -positive patients with first-line eradication failure were randomly assigned to two groups. The RAM group was administered rabeprazole 20 mg + amoxycillin 1500 mg + metronidazole 500 mg daily for 1 week. The RA group was administered rabeprazole 40 mg + amoxycillin 2000 mg daily for 2 weeks. Eradication of H. pylori infection was determined by 13C-urea breath testing at 8 weeks after completion of treatment. Prior to treatment, amoxycillin, clarithromycin and metronidazole susceptibility, and CYP2C19 phenotype status were determined. Results Eradication rates for the RAM and RA groups were 97% and 74%, respectively. Eradication rates were not influenced by CYP2C19 phenotype in either group. Eradication rates for clarithromycin-resistant patients were 100% in the RAM group and 77% in the RA group. Conclusions One week with RAM therapy and 2 weeks with RA therapy were effective as second-line eradication therapy for H. pylori infection; moreover, RAM was more effective than RA therapy. [source] High-dose ecabet sodium improves the eradication rate of Helicobacter pylori in dual therapy with lansoprazole and amoxicillinALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2000H. Kagaya The additive effect of ecabet sodium in combination with dual therapy on Helicobacter pylori eradication was evaluated. Methods: H. pylori -positive chronic gastritis patients were randomly assigned to one of the following three groups and medicated for 2 weeks. Group LA: dual therapy (lansoprazole 30 mg o.d. plus amoxicillin 750 mg b.d.). Group LA1E: dual therapy plus ecabet sodium (1 g b.d.). Group LA2E: dual therapy plus ecabet sodium (2 g b.d.). Patients were evaluated 4 weeks after the cessation of treatment by culture and 13C-urea breath test. Results: Seventy-one patients (mean age, 56.6 years; range, 26,79 years; 40 males, 31 females) were enrolled in this prospective, single-blind study, and 68 completed the protocol. The eradication rates per protocol patient were 43% in group LA, 62% in group LA1E, and 79% in group LA2E, and those on the intention-to-treat basis were 42% in group LA, 57% in group LA1E and 79% in group LA2E. The eradication rate in group LA2E was significantly higher than group LA (P=0.032 in per protocol, P=0.022 in intention-to-treat). Adverse effects were observed in 10 patients in this study. There were no severe adverse effects caused by ecabet sodium. Conclusion: High-dose ecabet sodium increases eradication rates of H. pylori in dual therapy with lansoprazole and amoxicillin. [source] Comparison of lansoprazole-based triple and dual therapy for treatment of Helicobacter pylori -related duodenal ulcer: an Asian multicentre double-blind randomized placebo controlled studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000Wong Bakcground : In Asian countries with limited resources, clarithromycin-based triple therapy may not be readily available. There are also few direct comparisons of different regimens in Asia. Aim : To compare two lansoprazole-based non-clarithromycin triple therapies and one dual therapy in a prospective double-blind placebo-controlled study of Helicobacter pylori eradication and duodenal ulcer healing. Methods : Fourteen centres in Asia participated in this study. Patients with acute duodenal ulcer who were H. pylori -positive were recruited. They were randomized to receive: (a) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and metronidazole 500 mg b.d. for 2 weeks (LAM-2 W), or (b) LAM for 1 week and placebo (LAM-1 W), or (c) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and placebo for 2 weeks (LA-2 W). Upper endoscopy was repeated at week 6 to check for duodenal ulcer healing. Symptoms and side-effects were recorded. Results : A total of 228 patients were recruited, and two patients took less than 50% of the drugs. H. pylori eradication rates (intention-to-treat) were 68 out of 82 (83%) with LAM-2 W, 55 out of 71 (78%) with LAM-1 W and 43 out of 75 (57%) with LA-2 W. There were significant differences (P=0.001) in eradication rates when comparing either LAM-2 W or LAM-1 W with LA-2 W. The eradication rate in patients with metronidazole resistant H. pylori strains were significantly lower than those with metronidazole sensitive strains (P=0.0001). The duodenal ulcer healing rates at week 6 were 85%, 85% and 72% in LAM-2 W, LAM-1 W and LA-2 W, respectively (P=0.065). Side-effects occurred in 13%, 11% and 9% in LAM-2 W, LAM-1 W and LA-2 W, respectively. H. pylori eradication and initial ulcer size were factors affecting duodenal ulcer healing. Conclusions : This Asian multicentre study showed that 1-week lansoprazole-based triple therapy without clarithromycin has similar efficacy in H. pylori eradication and ulcer healing compared with a 2-week regimen. Both triple therapies were significantly better than dual therapy in H. pylori eradication. Therefore, 1-week lansoprazole-based triple therapy is as safe and effective as 2-week therapy in eradication of H. pylori infection and healing of duodenal ulcer in these Asian centres. [source] Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000,2007,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2008Alexander M. Walker MD, DrPH Abstract Background The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices. Objectives To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas. Methods We conducted a retrospective cohort study of MI and CR in the PharMetrics database. We performed head-to-head comparisons using propensity-score-stratified Cox proportional hazards models, examining risks both on-treatment and during total follow-up before regimen switches. Results For the combined outcome (MI and CR), the crude rates per 1000 person years were 9 on monotherapy, 13 on dual therapy, and 21 on therapies combined with insulin. In the absence of insulin, regimens containing thiazolidinediones (TZDs) tended toward lower risk than comparable regimens containing sulfonylureas and higher risk than those containing metformin. The summary hazard ratio for rosiglitazone versus pioglitazone was 1.04 (95%CI: 0.94,1.14) for total follow-up and 1.05 (0.92,1.19) for on-treatment time. For MI, the hazard ratios were 1.07 (0.89,1.27) for total follow-up and 1.21 (0.95,1.54) for on-treatment time. Conclusions The present data indicate that the risk of CHD in patients using TZDs appears to lie between the risks associated with sulfonylureas and metformin. Neither the risk of MI and CR together nor the risk of MI alone was significantly different between rosiglitazone and pioglitazone. A nonsignificant observed excess risk of 21% for MI during on-treatment time will require combination with the results of other studies to provide a reliable assessment. Copyright © 2008 John Wiley & Sons, Ltd. [source] Cancer risks in thiazolidinedione users compared to other anti-diabetic agents,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2007Carol Koro PhD Abstract Purpose We conducted three nested case-control studies to evaluate the risk of breast, colon, and prostate cancers developing in patients exposed to thiazolidinediones (TZDs) compared with other anti-diabetic agents. Methods Cancer cases were matched to five controls by age, gender, calendar year, and time in the database from a cohort of 1,26,971 diabetic patients taking anti-diabetic medication in the US Integrated Healthcare Information Services database. Five hundred thirteen breast cancer cases were matched with 2557 controls, 408 cases of colon cancer were matched with 2027 controls and 643 cases of prostate cancer were matched with 3176 controls. Exposure to an anti-diabetic agent within 90 days preceding the index date was defined as recent exposure and at any time during the follow-up was defined as ever exposed. Results The adjusted odds ratios and 95%CI of cancer from ever exposure to TZDs compared to oral monotherapy, oral dual therapy, oral triple therapy, insulin monotherapy, insulin and oral therapy and all non-TZD anti-diabetic agents were, respectively for breast cancer: 0.91 (0.69,1.20), 0.80 (0.56,1.14), 0.87 (0.32,2.35), 1.27 (0.61,2.67), 0.71 (0.36,1.37), 0.89 (0.68,1.15); for colon cancer: 1.06 (0.80,1.40), 1.12 (0.77,1.63), 1.73 (0.39,7.78), 4.46 (1.05,19.00), 1.06 (0.50,2.26) 1.03 (0.80,1.32) and for prostate cancer: 1.08 (0.85,1.37), 0.89 (0.66,1.21); 0.82 (0.33,2.06); 1.80 (0.79,4.07), 1.10 (0.55,2.18), 1.04 (0.83,1.31). Results for exposure within 90 days of the date of the cancer were similar. Conclusions Our findings suggest that the effect of TZDs on the likelihood of development of the cancers studied (colon, prostate and breast) appears to be neutral and do not support a beneficial or deleterious effect of TZD on the cancers studied. Copyright © 2006 John Wiley & Sons, Ltd. [source] Liraglutide: new GLP-1 analogue for uncontrolled type 2 diabetesPRESCRIBER, Issue 23-24 2009MRPharmS, Steve Chaplin MSc Liraglutide (Victoza) is a new GLP-1 analogue given by once-daily injection for the treatment of type 2 diabetes not controlled by mono- or dual therapy with oral agents. In our New products review, Steve Chaplin presents the clinical data relating to its efficacy and adverse effects, and Dr Aftab Ahmad considers its potential place in therapy. Copyright © 2009 Wiley Interface Ltd [source] Antiretroviral therapy and preterm delivery,a pooled analysis of data from the United States and EuropeBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2010CL Townsend Please cite this paper as: Townsend C, Schulte J, Thorne C, Dominguez K, Tookey P, Cortina-Borja M, Peckham C, Bohannon B, Newell M, for the Pediatric Spectrum of HIV Disease Consortium, the European Collaborative Study and the National Study of HIV in Pregnancy and Childhood. Antiretroviral therapy and preterm delivery,a pooled analysis of data from the United States and Europe. BJOG 2010;117:1399,1410. Objective, To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women. Design, Combined analysis of data from three observational studies. Setting, USA and Europe. Population, A total of 19 585 singleton infants born to HIV-infected women, 1990,2006. Methods, Data from the Pediatric Spectrum of HIV Disease project (PSD), a US monitoring study, the European Collaborative Study (ECS), a consented cohort study, and the National Study of HIV in Pregnancy and Childhood (NSHPC), the United Kingdom and Ireland surveillance study. Main outcome measure, Preterm delivery rate (<37 weeks of gestation). Results, Compared with monotherapy, HAART was associated with increased preterm delivery risk in the ECS (adjusted odds ratio [AOR] 2.40, 95% CI 1.49,3.86) and NSHPC (AOR 1.43, 95% CI 1.10,1.86), but not in the PSD (AOR 0.92, 95% CI 0.67,1.26), after adjusting for relevant covariates. Because of heterogeneity, data were not pooled for this comparison, but heterogeneity disappeared when HAART was compared with dual therapy (P = 0.26). In a pooled analysis, HAART was associated with 1.5-fold increased odds of preterm delivery compared with dual therapy (95% CI 1.19,1.87, P = 0.001), after adjusting for covariates. Conclusions, Heterogeneity in the association between HAART and preterm delivery was not explained by study design, adjustment for confounders or a standard analytical approach, but may have been the result of substantial differences in populations and data collected. The pooled analysis comparing HAART with dual therapy showed an increased risk of preterm delivery associated with HAART. [source] | ||||||||||