Strategies for price reduction of HIV medicines under a monopoly situation in Brazil

ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

A narrative review on the reduction of effective dose to a paediatric patient by using different combinations of kVp, mAs and additional filtration whilst maintaining image quality

This paper reviews the literature for lowering of dose to paediatric patients through use of exposure factors and additional filtration. Dose reference levels set by The International Commission on Radiological Protection (ICRP) will be considered. Guidance was put in place in 1996 requires updating to come into line with modern imaging equipment. There is a wide range of literature that specifies that grids should not be used on paediatric patients. Although much of the literature advocates additional filtration, contrasting views on the relative benefits of using aluminium or copper filtration, and their effects on dose reduction and image quality can vary. Changing kVp and mAs has an effect on the dose to the patient and image quality. Collimation protects adjacent structures whilst reducing scattered radiation.

A new CuZ active form in the catalytic reduction of N2O by nitrous oxide reductase from Pseudomonas nautica

J Biol Inorg Chem (2010) 15:967–976 DOI 10.1007/s00775-010-0658-6

Reduction of morbidity in hepatosplenic Schistosomiasis mansoni after treatment with praziquantel: a long term study

Forty-two with hepatosplenic patients treated with praziquantel and followed up for 5 years. One half of the patients received a single 30 mg/kg dose and the other half, two doses of 25 mg/kg given 4 hrs apart. According to Hoffman and Kato-Katz stool exams, an 83.3% cure rate, was observed after twelve months. Stool egg counts in cases of incomplete cure were greatly reduced. Liver function, as assessed by serum levels of aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase activities as well as albumin and gamma globulin showed marked improvement after one year. Hepatomegaly was reduced in 81.0% of patients and splenomegaly in 78.8%. Spleen regression was complete in 15.1% of the total, and in 18.5% of those with compensated hepatosplenic disease. As a result of these observations, the authors recomend early treatment with anti-schistosomal medication, either oxamniquine or praziquantel, to halt progression of disease and reduce splenomegaly.

Reduction of spleen size in a child with Hyperreactive Malarious Splenomegaly (HMS) treated outside the Brazilian endemic area of malaria with only one course of quinine

We report the clinical picture, treatment and evolution of a child with hyperreactive malarious splenomegaly treated outside the endemic area of malaria. The patient presented gross splenomegaly, proceeded from an area where malaria is endemic, showed increased immunoglobulins levels, high antimalarial antibody titres and hepatic sinusoidal lymphocytosis. The child did not return to an area where malaria is endemic and showed a favorable response to only one course of quinine. The response of this patient to limited antimalarial therapy suggests the importance of reinfection with malaria in the development and maintenance of this syndrome.

Reduction of catheter-associated bloodstream infections through procedures in newborn babies admitted in a university hospital intensive care unit in Brazil

INTRODUCTION: Catheter-associated bloodstream infection (CA-BSI) is the most common nosocomial infection in neonatal intensive care units. There is evidence that care bundles to reduce CA-BSI are effective in the adult literature. The aim of this study was to reduce CA-BSI in a Brazilian neonatal intensive care unit by means of a care bundle including few strategies or procedures of prevention and control of these infections. METHODS: An intervention designed to reduce CA-BSI with five evidence-based procedures was conducted. RESULTS: A total of sixty-seven (26.7%) CA-BSIs were observed. There were 46 (32%) episodes of culture-proven sepsis in group preintervention (24.1 per 1,000 catheter days [CVC days]). Neonates in the group after implementation of the intervention had 21 (19.6%) episodes of CA-BSI (14.9 per 1,000 CVC days). The incidence of CA-BSI decreased significantly after the intervention from the group preintervention and postintervention (32% to 19.6%, 24.1 per 1,000 CVC days to 14.9 per 1,000 CVC days, p=0.04). In the multiple logistic regression analysis, the use of more than 3 antibiotics and length of stay >8 days were independent risk factors for BSI. CONCLUSIONS: A stepwise introduction of evidence-based intervention and intensive and continuous education of all healthcare workers are effective in reducing CA-BSI.

Reduction of QTc interval dispersion. Potential mechanism of cardiac protection of pyridostigmine bromide

OBJECTIVE: Parasympathetic dysfunction is an independent risk factor in individuals with coronary artery disease, and cholinergic stimulation is a potential therapeutical option. We determined the effects of pyridostigmine bromide, a reversible anticholinesterase agent, on electrocardiographic variables of healthy individuals. METHODS: We carried out a cross-sectional, double blind, randomized, placebo-controlled study. We obtained electrocardiographic tracings in 12 simultaneous leads of 10 healthy young individuals at rest before and after oral administration of 45 mg of pyridostigmine or placebo. RESULTS: Pyridostigmine increased RR intervals (before: 886±27 ms vs after: 1054±37 ms) and decreased QTc dispersion (before: 72±9ms vs after: 45±3ms), without changing other electrocardiographic variables (PR segment, QT interval, QTc, and QT dispersion). CONCLUSION: Bradycardia and the reduction in QTc dispersion induced by pyridostigmine may effectively represent a protective mechanism if these results can be reproduced in individuals with cardiovascular diseases.

Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

OBJECTIVE: To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. METHODS: By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. RESULTS: Before surgery, all hemodynamic variables were comparable among groups. After surgery, LV end-diastolic pressure increased and coronary driving pressure decreased significantly in the LMI compared with the sham group. LV dP/dt max and dP/dt min of both the SMI and LMI groups were statistically different from those of the sham group. CVF within non-MI interventricular septum and right ventricle did not differ between each MI group and the sham group. Otherwise, subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF correlated negatively with post-MI systemic blood pressure and coronary driving pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis identified post-MI coronary driving pressure as an independent predictor of SE CVF. CONCLUSION: LV remodeling in rats with MI is characterized by predominant SE collagen deposition in non-MI and results from a reduction in myocardial perfusion pressure occurring early on in the setting of MI.

Reverse Auction: A Potential Strategy for Reduction of Pharmacological Therapy Cost

Background:Polypharmacy is a significant economic burden.Objective:We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients.Methods:We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost.Results:The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05‑340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively.Conclusion:RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.

Interpolatory methods for model reduction of large-scale dynamical systems

Magdeburg, Univ., Fak. für Mathematik, Diss., 2013

Computational methods for model reduction of large-scale sparse structured descriptor systems

Magdeburg, Univ., Fak. für Mathematik, Diss., 2015

Reduction of periodic difference systems to linear or autonomous ones

We extend Floquet theory for reducing nonlinear periodic difference systems to autonomous ones (actually linear) by using normal form theory.

Reduction of small infrarenal abdominal aortic aneurysm expansion rate by statins.

BACKGROUND: To evaluate the effect of statins on the annual expansion rate (ER) of small infrarenal abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: All patients under regular surveillance for small AAA between January 2000 and September 2007, in the Department of Angiology, Lausanne University Hospital, were included. Inclusion criteria were baseline abdominal aortic diameter between 25 and 55 mm, at least two measurements of AAA diameter and a minimum follow up of 6 months. Patients with Marfan disease, infectious or inflammatory AAA, and patients with prior AAA repair were excluded. The influence of statin use and other factors on ER were examined by bivariate and multivariate analysis. RESULTS: Among 589 patients who underwent an abdominal aorta evaluation, 94 patients (89 % men, mean age 69.1 years) were finally included in the analysis. Baseline AAA size was 39.9 ± 7.7 mm (mean±SE) and 48.7 ± 8.4 mm at end of follow-up. Patients had a regular aneurysm size assessment during 38.5 ± 27.7 months. Mean ER was 3.59 mm/y (± 2.81). The 50 patients who were treated with statin during the study period had a lower ER compared to the 44 controls (2.91 vs 4.37 mm/year, p = 0.01). CONCLUSIONS: This study confirms the considerable individual variations in the AAA expansion rate, and emphasizes the need for regular aortic diameter assessments. In this study, patients treated with statin demonstrate a significant decrease in the ER compared to controls. This finding need to be evaluated in prospective interventional studies powered to demonstrate the potential benefit of statin treatment.

Genotype-level interactions determine the degree of reduction of leaf rust on wheat by seed application of beneficial Pseudomonas spp.

Some bacteria have the capacity to reduce incidence and severity of plant diseases either by inhibiting the pathogen or by modulating the resistance response of the plant. Plants dispose of different resistance mechanisms that are influenced by the biotic and abiotic environment. The present experiments explored the effects of biocontrol strains of Pseudomonas fluorescens on the resistance of wheat varieties against brown rust disease caused by Puccinia triticina. Root inoculation with biocontrol pseudomonads reduced the disease severity on the leaves. The plant response depended on the genotype of both the microbes and the wheat varieties, suggesting a straight interaction at the molecular level.