Trajetória de pessoas com AIDS em situação de vulnerabilidade social: à luz da história oral de vida

The epidemic caused by HIV presents a global, dynamic and unstable phenomenon, which depends on the individual and collective human behavior. Efforts to deconstruct the stigmatized image caused by infection of AIDS are still often associated with adoption of socially unacceptable behavior to be a circumscribed the susceptibilities of vulnerable individuals and communities to infection, illness and death by HIV. This study aimed to: narrate the trajectory of life of people with AIDS more vulnerable enrolled in the Municipal Social Assistance Parnamirim / RN. It is a study of qualitative, exploratory and descriptive approach, taking oral history of life as technical and methodological framework. The colony consisted of 186 people with AIDS. The network was comprised of 13 employees of both sexes, aged between 19 and 62 years old with positive diagnosis and agreed to voluntarily participate. After approval by the Ethics Committee of the Federal University of Rio Grande do Norte (CEP / UFRN), in the opinion No. 719,926 CAAE: 30408114.5.0000.5537 on 6 June 2014 data were collected from August to September 2014. The employees signed the Informed Consent and Informed and letter of assignment. Held transcribing the interviews and later returned to respondents to retest, ie so that they confer what allowed us to carry out transcreation after consecutive readings. The reports were analyzed through Bardin content analysis. Guiding the analysis of the accounts of employees, we find three themes: Prejudice and discrimination in living with AIDS; Reacting to the diagnosis and the accession process to antiretroviral treatment; and religious coping in people with AIDS. It can be concluded in this study, that employees have shown great emotional impact after positive diagnosis for HIV / AIDS, especially with regard to social life, the family ties, work and above all to the prejudice of society. Treatment with antiretroviral drugs was seen as a motivation to regain dreams and plans for a future once uncertain, and even if it is not a cure therapy, provided the employees improved quality of life.

Trajetória de pessoas com AIDS em situação de vulnerabilidade social: à luz da história oral de vida

The epidemic caused by HIV presents a global, dynamic and unstable phenomenon, which depends on the individual and collective human behavior. Efforts to deconstruct the stigmatized image caused by infection of AIDS are still often associated with adoption of socially unacceptable behavior to be a circumscribed the susceptibilities of vulnerable individuals and communities to infection, illness and death by HIV. This study aimed to: narrate the trajectory of life of people with AIDS more vulnerable enrolled in the Municipal Social Assistance Parnamirim / RN. It is a study of qualitative, exploratory and descriptive approach, taking oral history of life as technical and methodological framework. The colony consisted of 186 people with AIDS. The network was comprised of 13 employees of both sexes, aged between 19 and 62 years old with positive diagnosis and agreed to voluntarily participate. After approval by the Ethics Committee of the Federal University of Rio Grande do Norte (CEP / UFRN), in the opinion No. 719,926 CAAE: 30408114.5.0000.5537 on 6 June 2014 data were collected from August to September 2014. The employees signed the Informed Consent and Informed and letter of assignment. Held transcribing the interviews and later returned to respondents to retest, ie so that they confer what allowed us to carry out transcreation after consecutive readings. The reports were analyzed through Bardin content analysis. Guiding the analysis of the accounts of employees, we find three themes: Prejudice and discrimination in living with AIDS; Reacting to the diagnosis and the accession process to antiretroviral treatment; and religious coping in people with AIDS. It can be concluded in this study, that employees have shown great emotional impact after positive diagnosis for HIV / AIDS, especially with regard to social life, the family ties, work and above all to the prejudice of society. Treatment with antiretroviral drugs was seen as a motivation to regain dreams and plans for a future once uncertain, and even if it is not a cure therapy, provided the employees improved quality of life.

Duplicação rápida de prótese total: passo-a-passo

This study presents a simple, fast and low cost technique for fabrication new conventional dentures from the duplication of old prosthesis in use by the patient. Colorless acrylic resin was poured into the moulds obtained by duplication of prosthesis. With the replicas obtained a functional impressions using polyether should be performed and they are stabilized with occlusal registration in acrylic resin. The molds need to be castings and mounted on an semi-adjustable articulator. The artificial teeth are positioned with the assistance of a guide made condensation silicone to reproduce the positioning of the teeth of the old prosthesis and fixed with wax 7. After approval of the teeth on the trial in wax, without adjustment of the planes, the prosthesis may be processed in the laboratory. After occlusal adjustment in the articulator the same can be installed.

Acurácia dos indicadores clínicos do diagnóstico de enfermagem falta de adesão em pessoas vivendo com AIDS

In the early 1990s, a major milestone in the treatment of Acquired Immune Deficiency Syndrome was the development of highly active combination antiretroviral therapy. The great benefit generated by the use of this therapy was prolonging the survival of the people who got this disease, since it is no longer considered fatal, becoming a chronic condition. Despite improvements generated by this therapy, there are still many difficulties to be overcome. One is the patient adherence to their treatment, bringing challenges to services and health professionals. Hence the need for early identification of nursing diagnosis Lack of Accession so that solutions are sought by the nurse with the patient and his family. With this problem, adds to the difficulty of hospital nurses in inferring that diagnosis, especially in identifying their defining characteristics. In this context, the objective was to evaluate the accuracy of clinical indicators of nursing diagnosis Lack of Adherence to antiretroviral treatment for people living with the Acquired Immunodeficiency Syndrome. The research took place in two stages. The first consists of the evaluation of the diagnostic indicators in the study; and second, the diagnostic inference performed by specialist nurses. The first step took place in a referral hospital in the treatment of infectious diseases in the Northeast of Brazil, and data were collected through an instrument for carrying out history and physical examination and analyzed for the presence or absence of the diagnostic indicators. In the second stage, the data were sent to experts, who judged the presence or absence of the diagnosis in the studied clientele. The project was submitted to the Ethics Committee of the Federal University of Rio Grande do Norte, obtaining approval with the General Certificate for Ethics Assessment (CAAE) No 46206215.3.0000.5537. Data were analyzed using descriptive and inferential statistics. Test were used Fisher's exact, chi-square test of Pearson and logistic regression. Since the accuracy of clinical indicators was measured by sensitivity, specificity, predictive values, likelihood ratios. As a result, we identified the presence of diagnosis Lack of Accession on 69% (n = 78) of the study patients. The defining characteristics that showed statistically significant association with the diagnosis studied were: lack of adherence behavior, complications related to development, missing scheduled appointments, failure to achieve results, and exacerbation of symptoms. The characteristic with greater sensitivity was missing scheduled appointments and the highest specificity behavior of noncompliance. The logistic regression showed as predictors for the diagnosis Lack of Accession: lack of adherence behavior, missing scheduled appointments, failure to achieve results, and exacerbation of symptoms. It was concluded that the identification of clinical indicators accurately enabled a good prediction of the nursing diagnosis Lack of Accession on people living with the Acquired Immune Deficiency Syndrome, helping nurses develop early on strategies for promoting adherence to the use of antiretrovirals.

Acurácia dos indicadores clínicos do diagnóstico de enfermagem falta de adesão em pessoas vivendo com AIDS

In the early 1990s, a major milestone in the treatment of Acquired Immune Deficiency Syndrome was the development of highly active combination antiretroviral therapy. The great benefit generated by the use of this therapy was prolonging the survival of the people who got this disease, since it is no longer considered fatal, becoming a chronic condition. Despite improvements generated by this therapy, there are still many difficulties to be overcome. One is the patient adherence to their treatment, bringing challenges to services and health professionals. Hence the need for early identification of nursing diagnosis Lack of Accession so that solutions are sought by the nurse with the patient and his family. With this problem, adds to the difficulty of hospital nurses in inferring that diagnosis, especially in identifying their defining characteristics. In this context, the objective was to evaluate the accuracy of clinical indicators of nursing diagnosis Lack of Adherence to antiretroviral treatment for people living with the Acquired Immunodeficiency Syndrome. The research took place in two stages. The first consists of the evaluation of the diagnostic indicators in the study; and second, the diagnostic inference performed by specialist nurses. The first step took place in a referral hospital in the treatment of infectious diseases in the Northeast of Brazil, and data were collected through an instrument for carrying out history and physical examination and analyzed for the presence or absence of the diagnostic indicators. In the second stage, the data were sent to experts, who judged the presence or absence of the diagnosis in the studied clientele. The project was submitted to the Ethics Committee of the Federal University of Rio Grande do Norte, obtaining approval with the General Certificate for Ethics Assessment (CAAE) No 46206215.3.0000.5537. Data were analyzed using descriptive and inferential statistics. Test were used Fisher's exact, chi-square test of Pearson and logistic regression. Since the accuracy of clinical indicators was measured by sensitivity, specificity, predictive values, likelihood ratios. As a result, we identified the presence of diagnosis Lack of Accession on 69% (n = 78) of the study patients. The defining characteristics that showed statistically significant association with the diagnosis studied were: lack of adherence behavior, complications related to development, missing scheduled appointments, failure to achieve results, and exacerbation of symptoms. The characteristic with greater sensitivity was missing scheduled appointments and the highest specificity behavior of noncompliance. The logistic regression showed as predictors for the diagnosis Lack of Accession: lack of adherence behavior, missing scheduled appointments, failure to achieve results, and exacerbation of symptoms. It was concluded that the identification of clinical indicators accurately enabled a good prediction of the nursing diagnosis Lack of Accession on people living with the Acquired Immune Deficiency Syndrome, helping nurses develop early on strategies for promoting adherence to the use of antiretrovirals.

Proposta de um sistema de avaliação de desempenho para o Restaurante Universitário da UFRN

The aim of this study was to propose a Performance Evaluation System for outsourced employees of the University Restaurant of the Federal University of Rio Grande do Norte to supply the lack of evaluative instruments. According to Provision of Services Contract nº050/2010 and nº055/2011 of FURN with SAFE LOCAÇÃO DE MÃO DE OBRA LTDA ME, it is the hired company to promote periodic functional performance evaluation of the outsourced employees, but this is not done. The performance evaluation process serves to evaluate if the employees are making their tasks according to the organizations’ objectives and goals, besides that helps to find service failures and capacity of employees demands, thus contributing to improve work conditions and the global performance of the organizations. To elaborate the proposal of evaluation, it was chosen an action research with the participation of all stakeholders, employees and managers from UR. On data collect, first, outsourced employees and management servers were interviewed, in order to raise existing perceptions about performance evaluation aspects. From these data and the work routine observation, a proposal of performance evaluation was elaborated, that was appreciated, criticized and adjusted by the actors involved (employees and managers) to the final formulation of the instrument. This study also presents the necessary steps to the implementation of the Performance Evaluation System. The proposed Performance Evaluation System can be applied to the FURN assuming this process, after modification of contract terms and the approval by the ADCON. It also can serve as an example to others units that works with the provision of outsourced services, enabling so the performance evaluation to be part of the management policy of all people working in FURN.

Articulação entre saúde mental infanto-juvenil e atenção básica em Natal-RN: limites e possibilidades

In the case of Brazilian Psychiatric Reformation, mental health juvenile reveals itself as a great challenge, with major gaps in terms of needs, services and actions on mental illness in children and adolescents. This research is a qualitative study of descriptive and exploratory, having to analyze the actions and practices of mental health juvenile articulated between the Psychosocial Care Center juvenile (Caps i) and the basic care in Natal-RN, and specific, identify the limits and possibilities for an important precedent of the care network. After submission to the Research Ethics Committee (CEP) of the University Hospital Onofre Lopes (HUOL) of the Federal University of Rio Grande do Norte (UFRN) obtained approval contained in opinion number 777.067 / 2014. For the data collection, it was initially carried out a documentary research in the Municipal Health Department of Christmas about the phenomenon under study, and subsequently, applied semi-structured interviews with the subjects of the research, which were workers Caps i of Natal-RN. The analysis was woven as the thematic analysis technique, understood within the method of content analysis. The results and discussions were organized by categories and subcategories, namely: CATEGORY 1: Limits and weaknesses in the linkage between the Caps i and basic care, with the subcategories: 1.1 Lack of specialized services and devices articulators in network, 1.2 The diversity of situations in the demand juvenile assisted; CATEGORY 2: possibilities for an effective network, with the subcategory: 2.1 Intersectoral collaboration as a strategy for solving attention. The analysis revealed that the integration and coordination of mental health services juvenile and primary care in the city of Natal-RN, has incipient initiatives and/or inadequate for the resolvability intersectoral, where the devices of attention to health involved cannot establish bonds effective and long-lasting in the perspective of co-responsibility and sharing of care. On the other hand, it appears that the existing shares and practiced, configure an exercise in approximation to the dialog between mental health juvenile and basic care. It is highlighted that the shared care and the establishment of intersectoral collaboration within and outside of the health sector is possibility of facilitating the necessary dialog between the services and professionals involved, thus, enabling a better prospect of resolvability of the Network of Psychosocial Care for the youth in reality being investigated.

Magnitude da morbidade relacionada ao trabalho no Rio Grande do Norte

Diseases and disorders related to work sets up an important public health problem in Brazil and worldwide. However, the reality of these diseases still constitutes a gap with regard to its characterization and epidemiological situation, especially in Brazil. In this context, this study aims to analyze the magnitude of morbidity related to work from the injuries and illnesses reported by Health the Diseases Notifiable of Health of the State Public River Health Department worker Reference Center Information System services Grande do Norte from 2007 to 2014. It is ecological study, quantitative cross-sectional study in which the analysis unit of the municipalities of Rio Grande do Norte. Data were collected from the state base of Diseases Notifiable Information System Centre of the Secretariat of State Workers' Health Reference Public Health of Rio Grande do Norte, between March and June 2015, after the approval of the Committee of Ethics in Research of the Federal University of Rio Grande do Norte, Opinion 014/2014. The population was represented by the universe of cases of diseases and disorders related to work that were reported and shut down the system from 2007 to 2014. Data were analyzed using descriptive and inferential statistics, presented in tables, graphs, charts and figures. For this, we used the Microsoft Excel 2007 and SPSS version 20.0. To check the significance level we opted for the application of the chi-square or Fisher tests. We adopted the significance level of p <0.05. Of the 10,161 cases of diseases related to the reported work, the biological work accidents had the highest percentage (52.84%) followed by serious occupational accidents (37.49%). For diseases, the highlights were musculoskeletal (4.82%), mental disorders (2.19%) and exogenous intoxication (1.97%). Among men, there was a predominance of major accidents (91.80%), mental disorders (70.00%) and exogenous poisoning (52.84%). Women were most affected by biological accidents (77.50%) and musculoskeletal diseases (64.10%). Among workers who have suffered injuries predominated mulatto (%), mean age of 35.86 years, low education (%) and workers in the formal sector (%). Among the accidents, biological (n = 5,369) accounted for 52.84% of cases occurred predominantly among nursing professionals (48.31%). The percutaneous exposure was the most frequent (73.05%) and the occurrence of circumstances was improper disposal of sharps (45.28%), the needle the most common agent (66.62%) and the organic material was blood (72.99%). Most injured workers were vaccinated against hepatitis B (68.13%), but no information as to the assessment of the vaccine response. In the course of the disease predominated ignored the situation with loss of monitoring of clinical follow-up (55.62%). There was also an increase in the notification of serious industrial accidents predominantly male (91.80%) workers aged 25-44 years (54.3%) and typical accidents (76.3%). The temporary disability was the most common outcome (55.53%) and hand the most affected part (33.00%); the mining and construction industry had the highest number of cases (25.1%) in registered employee (34.2%). The findings of this study show a positive result in relation to increased mandatory reporting of injuries and illnesses related to work together to health services that meet victimized workers, towards the occurrence of knowledge of these accidents for decision making in public plans and policies of health. However, the information system still needs improvement in both the coverage and the quality of the data to demonstrate with greater reliability the magnitude of events to support the planning of workers' health into shares in the state.

Perceptions of practitioners : Managing marine protected areas for climate change resilience

Acknowledgements This research was supported and funded by ClimateXChange. ClimateXChange is a collaborative initiative between Scottish research and higher education institutes and is funded by the Scottish Government. The authors would like to thank all the participants who agreed to be interviewed for this study. Ethics approval number 2013001 from University of Glasgow.

Prior Antithrombotic Use is Associated with Favorable Mortality and Functional Outcomes in Acute Ischemic Stroke

Sources of Funding The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. These funding agencies did not participate in design or analysis, manuscript preparation, or approval of this study.

Whey protein isolate decreases murine stomach weight and intestinal length and alters the expression of Wnt signalling-associated genes

Acknowledgements K. N. N. was supported by the Teagasc Vision Programme on Obesity (RMIS5974). L. M. was supported by the Teagasc Walsh Fellowship. J. R. S. was supported by a 1000-talents professorship from the Chinese government. The funding bodies had no input on the design of the study or in the interpretation of the data. The authors’ contributions are as follows: L. M., J. R. S., J. F. C. and K. N. N. designed the study; K. N. N. and J. F. C. obtained ethical approval for the study; L. M. performed the experiments; L. M. and J. R. S. analysed the data; L. M. generated the figures. All authors contributed to the drafting of the manuscript. All authors approved the final version for submission. The authors declare that there is no competing interest.

Radiotherapy Treatment Assessment using DCE-MRI

Abstract

The goal of modern radiotherapy is to precisely deliver a prescribed radiation dose to delineated target volumes that contain a significant amount of tumor cells while sparing the surrounding healthy tissues/organs. Precise delineation of treatment and avoidance volumes is the key for the precision radiation therapy. In recent years, considerable clinical and research efforts have been devoted to integrate MRI into radiotherapy workflow motivated by the superior soft tissue contrast and functional imaging possibility. Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive technique that measures properties of tissue microvasculature. Its sensitivity to radiation-induced vascular pharmacokinetic (PK) changes has been preliminary demonstrated. In spite of its great potential, two major challenges have limited DCE-MRI’s clinical application in radiotherapy assessment: the technical limitations of accurate DCE-MRI imaging implementation and the need of novel DCE-MRI data analysis methods for richer functional heterogeneity information.

This study aims at improving current DCE-MRI techniques and developing new DCE-MRI analysis methods for particular radiotherapy assessment. Thus, the study is naturally divided into two parts. The first part focuses on DCE-MRI temporal resolution as one of the key DCE-MRI technical factors, and some improvements regarding DCE-MRI temporal resolution are proposed; the second part explores the potential value of image heterogeneity analysis and multiple PK model combination for therapeutic response assessment, and several novel DCE-MRI data analysis methods are developed.

I. Improvement of DCE-MRI temporal resolution. First, the feasibility of improving DCE-MRI temporal resolution via image undersampling was studied. Specifically, a novel MR image iterative reconstruction algorithm was studied for DCE-MRI reconstruction. This algorithm was built on the recently developed compress sensing (CS) theory. By utilizing a limited k-space acquisition with shorter imaging time, images can be reconstructed in an iterative fashion under the regularization of a newly proposed total generalized variation (TGV) penalty term. In the retrospective study of brain radiosurgery patient DCE-MRI scans under IRB-approval, the clinically obtained image data was selected as reference data, and the simulated accelerated k-space acquisition was generated via undersampling the reference image full k-space with designed sampling grids. Two undersampling strategies were proposed: 1) a radial multi-ray grid with a special angular distribution was adopted to sample each slice of the full k-space; 2) a Cartesian random sampling grid series with spatiotemporal constraints from adjacent frames was adopted to sample the dynamic k-space series at a slice location. Two sets of PK parameters’ maps were generated from the undersampled data and from the fully-sampled data, respectively. Multiple quantitative measurements and statistical studies were performed to evaluate the accuracy of PK maps generated from the undersampled data in reference to the PK maps generated from the fully-sampled data. Results showed that at a simulated acceleration factor of four, PK maps could be faithfully calculated from the DCE images that were reconstructed using undersampled data, and no statistically significant differences were found between the regional PK mean values from undersampled and fully-sampled data sets. DCE-MRI acceleration using the investigated image reconstruction method has been suggested as feasible and promising.

Second, for high temporal resolution DCE-MRI, a new PK model fitting method was developed to solve PK parameters for better calculation accuracy and efficiency. This method is based on a derivative-based deformation of the commonly used Tofts PK model, which is presented as an integrative expression. This method also includes an advanced Kolmogorov-Zurbenko (KZ) filter to remove the potential noise effect in data and solve the PK parameter as a linear problem in matrix format. In the computer simulation study, PK parameters representing typical intracranial values were selected as references to simulated DCE-MRI data for different temporal resolution and different data noise level. Results showed that at both high temporal resolutions (<1s) and clinically feasible temporal resolution (~5s), this new method was able to calculate PK parameters more accurate than the current calculation methods at clinically relevant noise levels; at high temporal resolutions, the calculation efficiency of this new method was superior to current methods in an order of 102. In a retrospective of clinical brain DCE-MRI scans, the PK maps derived from the proposed method were comparable with the results from current methods. Based on these results, it can be concluded that this new method can be used for accurate and efficient PK model fitting for high temporal resolution DCE-MRI.

II. Development of DCE-MRI analysis methods for therapeutic response assessment. This part aims at methodology developments in two approaches. The first one is to develop model-free analysis method for DCE-MRI functional heterogeneity evaluation. This approach is inspired by the rationale that radiotherapy-induced functional change could be heterogeneous across the treatment area. The first effort was spent on a translational investigation of classic fractal dimension theory for DCE-MRI therapeutic response assessment. In a small-animal anti-angiogenesis drug therapy experiment, the randomly assigned treatment/control groups received multiple fraction treatments with one pre-treatment and multiple post-treatment high spatiotemporal DCE-MRI scans. In the post-treatment scan two weeks after the start, the investigated Rényi dimensions of the classic PK rate constant map demonstrated significant differences between the treatment and the control groups; when Rényi dimensions were adopted for treatment/control group classification, the achieved accuracy was higher than the accuracy from using conventional PK parameter statistics. Following this pilot work, two novel texture analysis methods were proposed. First, a new technique called Gray Level Local Power Matrix (GLLPM) was developed. It intends to solve the lack of temporal information and poor calculation efficiency of the commonly used Gray Level Co-Occurrence Matrix (GLCOM) techniques. In the same small animal experiment, the dynamic curves of Haralick texture features derived from the GLLPM had an overall better performance than the corresponding curves derived from current GLCOM techniques in treatment/control separation and classification. The second developed method is dynamic Fractal Signature Dissimilarity (FSD) analysis. Inspired by the classic fractal dimension theory, this method measures the dynamics of tumor heterogeneity during the contrast agent uptake in a quantitative fashion on DCE images. In the small animal experiment mentioned before, the selected parameters from dynamic FSD analysis showed significant differences between treatment/control groups as early as after 1 treatment fraction; in contrast, metrics from conventional PK analysis showed significant differences only after 3 treatment fractions. When using dynamic FSD parameters, the treatment/control group classification after 1st treatment fraction was improved than using conventional PK statistics. These results suggest the promising application of this novel method for capturing early therapeutic response.

The second approach of developing novel DCE-MRI methods is to combine PK information from multiple PK models. Currently, the classic Tofts model or its alternative version has been widely adopted for DCE-MRI analysis as a gold-standard approach for therapeutic response assessment. Previously, a shutter-speed (SS) model was proposed to incorporate transcytolemmal water exchange effect into contrast agent concentration quantification. In spite of richer biological assumption, its application in therapeutic response assessment is limited. It might be intriguing to combine the information from the SS model and from the classic Tofts model to explore potential new biological information for treatment assessment. The feasibility of this idea was investigated in the same small animal experiment. The SS model was compared against the Tofts model for therapeutic response assessment using PK parameter regional mean value comparison. Based on the modeled transcytolemmal water exchange rate, a biological subvolume was proposed and was automatically identified using histogram analysis. Within the biological subvolume, the PK rate constant derived from the SS model were proved to be superior to the one from Tofts model in treatment/control separation and classification. Furthermore, novel biomarkers were designed to integrate PK rate constants from these two models. When being evaluated in the biological subvolume, this biomarker was able to reflect significant treatment/control difference in both post-treatment evaluation. These results confirm the potential value of SS model as well as its combination with Tofts model for therapeutic response assessment.

In summary, this study addressed two problems of DCE-MRI application in radiotherapy assessment. In the first part, a method of accelerating DCE-MRI acquisition for better temporal resolution was investigated, and a novel PK model fitting algorithm was proposed for high temporal resolution DCE-MRI. In the second part, two model-free texture analysis methods and a multiple-model analysis method were developed for DCE-MRI therapeutic response assessment. The presented works could benefit the future DCE-MRI routine clinical application in radiotherapy assessment.

Extended-release ranolazine: critical evaluation of its use in stable angina.

Coronary heart disease is the major cause of morbidity and mortality throughout the world, and is responsible for approximately one of every six deaths in the US. Angina pectoris is a clinical syndrome characterized by discomfort, typically in the chest, neck, chin, or left arm, induced by physical exertion, emotional stress, or cold, and relieved by rest or nitroglycerin. The main goals of treatment of stable angina pectoris are to improve quality of life by reducing the severity and/or frequency of symptoms, to increase functional capacity, and to improve prognosis. Ranolazine is a recently developed antianginal with unique methods of action. In this paper, we review the pharmacology of ranolazine, clinical trials supporting its approval for clinical use, and studies of its quality of life benefits. We conclude that ranolazine has been shown to be a reasonable and safe option for patients who have refractory ischemic symptoms despite the use of standard medications (for example, nitrates, beta-adrenergic receptor antagonists, and calcium channel antagonists) for treatment of anginal symptoms, and also provides a modestly improved quality of life.

Innovation in the pharmaceutical industry: New estimates of R&D costs.

The research and development costs of 106 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug and biologics development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per approved new compound is $1395 million (2013 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 10.5% yields a total pre-approval cost estimate of $2558 million (2013 dollars). When compared to the results of the previous study in this series, total capitalized costs were shown to have increased at an annual rate of 8.5% above general price inflation. Adding an estimate of post-approval R&D costs increases the cost estimate to $2870 million (2013 dollars).