Effects of antihypertensive agents on the quality of life in diabetic hypertensive patients: A prospective study.

Background: Diabetes mellitus is a chronic noncommunicable disease, and hypertension (HT) is the most common comorbidity which affects their quality of life (QoL). Aim: The aim of the study was to assess the effects of antihypertensive agents (viz., amlodipine, ramipril, telmisartan, and ramipril with telmisartan) on the blood pressure (BP) and QoL. Methodology: It was an open-labeled prospective intention-to-treat study done in diabetic hypertensive patients (CTRI/2016/10/007340). Patients were randomly assigned antihypertensive agents, namely, amlodipine, ramipril, telmisartan, and a combination of ramipril with telmisartan (RT) in four groups. They were evaluated for BP, blood sugar level, and QoL at baseline and 24th week. Results: After 24 weeks of therapy, systolic BP (SBP) and diastolic BP (DBP) were significantly reduced in all groups. In amlodipine, there was a mean percentage fall of SBP by 15.85% (confidence interval [CI]: 21.38-28.13) and DBP by 11.22% (CI: 8.41-12.70); in ramipril - 14.4% (CI: 18.61-25.15) and 12.4% (CI 8.88-13.99); telmisartan - 18.4% (CI: 24.89-10.79) and 14.6% (CI 10.79-16.24); and in RT group, SBP 17.7% (CI: 23.38-29.18) and DBP 12.4% (CI: 9.05-13.02). QoL score increased by 30.56% (CI: 14.30-10.90), 30.94% (CI: 14.21-10.68), 28.07% (CI: 14.89-11.20), and 28.84% (CI: 15.49-11.77), in respective groups (P < 0.0001, each). However, they were nonsignificant between the study groups (P > 0.05). Conclusion: Amlodipine, ramipril, telmisartan, and a combination of RT are equally effective to improve BP and QoL among diabetic hypertensive patients. However, amlodipine and telmisartan lacked in dry cough and more tolerable than the ramipril and RT therapy. Henceforth, amlodipine and telmisartan are better choice to control HT among DM patients.

Modulation of serum concentrations of melatonin by carbamazepine and valproate.

Evidence has accumulated about the involvement of reactive oxygen species (ROS) in epilepsy. The neuromodulator melatonin has been shown to reduce oxidative stress in various animal models due to its free radical scavenging properties. The present study investigated whether carbamazepine and valproate alter serum concentrations of melatonin. Epileptic children were randomly assigned to receive carbamazepine/ valproate monotherapy till 22 patients were recruited in the study. At the tenth day, in the evening, samples were drawn for baseline endogenous melatonin estimation. The patients were then administered exogenous melatonin, and repeat samples were drawn after 30 minutes. Serum levels of melatonin were estimated using Melatonin ELISA kits. The median levels of melatonin were 165.0 pg/ml (Range 50.0-350.0) in CBZ+MEL group and 78.0 pg/ml (Range 13.0-260.0) in the VPA+MEL group. The observed difference in melatonin levels could be attributed to the difference in antiepileptic drugs, additive increase in reactive oxygen species due to disease combined with carbamazepine, or possibly to a difference in melatonin kinetics in conditions of oxidative stress.

Biological response modifiers in cancer.

We have seen a surge in the use of immunotherapy for the treatment of cancer. Biological response modifiers can act passively by enhancing the immunologic response to tumor cells or actively by altering the differentiation/growth of tumor cells. Active immunotherapy with cytokines such as interferons (IFNs) and interleukins (IL-2) is a form of nonspecific active immune stimulation. The use of IL-2 has recently been approved by the United States Food and Drug Administration (FDA) for the treatment of renal cell carcinoma and metastatic colorectal cancer. Considerable success has been achieved with the use of immunotherapy, especially in the area of passive immunotherapy using monoclonal antibodies--in particular, radiolabeled monoclonal antibodies. In addition to the various monoclonal antibodies that have been used in clinical trials, other strategies such as the use of antiangiogenic agents and matrix metalloprotease inhibitors (MMPIs) have also met with some success. Recently, the FDA approved bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, for the treatment of metastatic melanoma. This review also sheds light on the various angiogenesis inhibitors in clinical trials, the increasing use of thalidomide in cancer, and the upcoming potential cancer vaccines designed to activate cell-mediated immune responses against tumor antigens.

Add-on melatonin improves sleep behavior in children with epilepsy: randomized, double-blind, placebo-controlled trial.

This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire. Of the 31 patients, 16 randomly received add-on melatonin, whereas 15 received add-on placebo. The questionnaire showed good internal consistency in our patient population (Cronbach's alpha = .83). The percentage decrease in the median total sleep score was 24.4 (range 0.0-34.9) in the valproate + melatonin group compared with 14.0 (range -2.2-18.8) in the valproate + placebo group, the difference being statistically significant (P < .05). The median percentage decrease in the parasomnias score was 60 (range 0.0-70.8) in the valproate + melatonin group compared with 36.4 (range 0.0-63.2) in the valproate + placebo group, the difference being statistically significant (P < .05). There was no significant difference between the percentage decrease in the daytime drowsiness scores and sleep fragmentation scores. Parent-child interaction subscale scores were not significantly different between age groups. The age at onset of seizures and the type of seizures did not correlate significantly to the total sleep scores. Given that sleep problems are known to complicate epilepsy, add-on melatonin, which has a wide safety window, can be of promise in the pharmacotherapy of pediatric epilepsy.

Effects of add-on melatonin administration on antioxidant enzymes in children with epilepsy taking carbamazepine monotherapy: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Melatonin has been shown to exhibit antioxidant, antiexcitotoxic, and free radical-scavenging properties in various animal models. The study was designed to assess its effects on the blood levels of antioxidant enzymes in children with epilepsy receiving carbamazepine (CBZ). METHODS: In a double-blind, randomized, parallel-group, placebo-controlled trial, we assessed the effect of add-on melatonin (6-9 mg/day for 14 days) on the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GRd) in 31 children with epilepsy receiving CBZ monotherapy, who were seizure free at least for the last 6 months. The interaction of melatonin with CBZ and its active metabolite, carbamazepine-10, 11-epoxide (CBZ-E), also was studied. RESULTS: An increase in GRd activity was noted in the melatonin group as compared with a decrease of the same enzyme in the placebo group. Changes in GPx activity failed to reach statistical significance. No significant changes were found in the serum levels of CBZ and CBZ-E in either group. CONCLUSIONS: The study suggests that melatonin exerts antioxidant activity in patients with epilepsy receiving CBZ therapy.

A randomized, double-blind, placebo controlled trial of melatonin add-on therapy in epileptic children on valproate monotherapy: effect on glutathione peroxidase and glutathione reductase enzymes.

AIMS: To compare the effect of add-on melatonin with placebo on the antioxidant enzymes (glutathione peroxidase and glutathione reductase) in epileptic children on valproate monotherapy. METHODS: In a double-blind, randomized, placebo controlled trial, the effect of add-on melatonin administration on the antioxidant enzymes in epileptic children on valproate (VPA) monotherapy was assessed. A total of 31 patients met the entry criteria. 16 patients were randomly allocated to receive add-on melatonin, and 15 to receive add-on placebo. Blood samples (5 ml) were collected just before the morning dose of valproate for baseline values of glutathione peroxidase and glutathione reductase enzymes, and then after 14 days of add-on melatonin/placebo. Blood was then centrifuged at 3500 r.p.m., serum separated and stored in deep freezer at -20 degrees C until assay of glutathione reductase. Heparinized blood was collected and stored at -20 degrees C in eppendorfs in the deep freezer for assay of glutathione peroxidase. All activity assays were performed on the Ames (Technicon) RA 50 chemistry analyser. RESULTS: Fifteen patients in the add-on melatonin group and 14 patients in the add-on placebo group were finally assessed. There was an increase in the activity of antioxidant enzymes, glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rd), in the add-on melatonin (MEL) group as compared with a reduction in the same in the add-on placebo group (P). After the addition of melatonin/placebo in the respective groups, there was a 7.5% decrease in GSH-Px in the valproate + placebo group, whereas a 11.9% increase in the valproate + melatonin group was observed, the difference between the groups being not statistically significant (P = 0.29). On administration of melatonin/placebo, the post-treatment concentrations of GSSG-Rd in the valproate + placebo group decreased from 92.0 U l(-1) to 67.0 U l(-1) and increased from 82.0 U l(-1) to 113.0 U l(-1), in the valproate + melatonin group, respectively, the difference between them being statistically significant (P = 0.05). The percentage change in the values of GSSG-Rd in the two groups was statistically significant (P = 0.005). CONCLUSIONS: Melatonin exerts neuroprotection due to its antioxidant, antiexcitotoxic and free radical scavenging properties within the central nervous system. Melatonin, thus, as an adjunct, can be a putative neuroprotector in conditions involving oxidative stress like epilepsies.

Pharmacoeconomics.

Pharmacoeconomics focuses on the costs and benefits of drug therapy and pharmacoeconomic evaluations provide a basis for resource allocation and utilization. It is increasingly becoming important for health policy decision-making. A pharmacoeconomic evaluation may be conducted as an economic assessment incorporated into clinical trials. Such trials should compare the new drug/procedure with an older drug or existing intervention. Four techniques are used for economic evaluation, namely, cost-minimization analysis, cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis. The choice of the evaluation method depends on the nature of outcomes and the context in which the choices need to be made. Pharmacoeconomics is a young science that will improve with application. Its need is undeniable, especially in developing countries.

Add-on melatonin improves quality of life in epileptic children on valproate monotherapy: a randomized, double-blind, placebo-controlled trial.

This randomized, double-blind, placebo-controlled study in epileptic children aged 3-12 years evaluated the effects of add-on melatonin administration on the quality of life of these children on sodium valproate (VPA) monotherapy using a parental questionnaire. Quality of Life in Childhood Epilepsy is a questionnaire designed to assess a variety of age-relevant domains such as physical function, emotional well-being, cognitive function, social function, behavior, and general health. Of the 31 patients, 16 randomly received add-on melatonin (MEL), whereas 15 received add-on placebo (P). The questionnaire had good internal consistency reliability, because for most of the multi-item scales Cronbach's alpha reliability exceeded 0.5 (range: 0.59-0.94). To our knowledge, this is the first study assessing quality of life in epileptic children with add-on melatonin administration in the form of a randomized, double-blind, placebo-controlled trial. The study suggests a potential use of melatonin as an adjunct to antiepileptic therapy due to its diverse spectrum of action as an antioxidant, neuroprotector, and free radical scavenger, thus offering the advantage of reducing oxidant stress and subsequent damage. The beneficial effects of melatonin on sleep, its wide safety window, and its ability to cross the blood-brain barrier have the potential to improve quality of life in pediatric epilepsy.