Prevalence and clinical outcomes of episodes of ventilator-associated pneumonia caused by SPM-1-producing and non-producing imipenem-resistant Pseudomonas aeruginosa

INTRODUCTION: Pseudomonas aeruginosa is a leading cause of ventilator-associated pneumonia (VAP) and exhibits high rates of resistance to several antimicrobial drugs. The carbapenens are usually the drugs of choice against this microorganism. However, the carbapenem resistance has increased among these strains worldwide. The presence of metallo-β-lactamases (MBL) has been pointed out as a major mechanism of resistance among these strains. No previous study addressed outcomes of respiratory infections caused by these strains. METHODS: Our group sought to analyze the epidemiology and clinical outcomes of patients with VAP caused by imipenem-resistant P. aeruginosa. A total of 29 clinical isolates of carbapenem-resistant Pseudomonas aeruginosa were screened for metallo-β-lactamase (MBL) genes. RESULTS: Demographic and clinical variables were similar between the SPM-1-producing and non-SPM-1-producing group. Five (17.2%) isolates were positive for blaSPM-1. No other MBL gene was found. All patients were treated with polymyxin B. The infection-related mortality was 40% and 54.2% for SPM-1-producing and -non-producing isolates, respectively. CONCLUSIONS: There were no differences in epidemiological and clinical outcomes between the two groups.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

Effects of PDE type 5 inhibitors on Left Ventricular Diastolic Dysfunction in Resistant Hypertension

Resistant hypertension (RHTN) is a multifactorial disease characterized by blood pressure (BP) levels above goal (140/90 mmHg) in spite of the concurrent use of three or more antihypertensive drugs of different classes. Moreover, it is well known that RHTN subjects have high prevalence of left ventricular diastolic dysfunction (LVDD), which leads to increased risk of heart failure progression. This review gathers data from studies evaluating the effects of phosphodiesterase-5 (PDE-5) inhibitors (administration of acute sildenafil and short-term tadalafil) on diastolic function, biochemical and hemodynamic parameters in patients with RHTN. Acute study with sildenafil treatment found that inhibition of PDE-5 improved hemodynamic parameters and diastolic relaxation. In addition, short-term study with the use of tadalafil demonstrated improvement of LVDD, cGMP and BNP-32 levels, regardless of BP reduction. No endothelial function changes were observed in the studies. The findings of acute and short-term studies revealed potential therapeutic effects of IPDE-5 drugs on LVDD in RHTN patients.

Anti-leishmanial activity of alkaloidal extract from Aspidosperma ramiflorum

Infections due to protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials (SbV), which present renal and cardiac toxicity. Besides, the precise chemical structure and mechanism of action of these drugs are unknown up to date. In order to find new drugs against leishmaniasis, we have been studying extracts of Brazilian trees. In the present study, we have evaluated the effectiveness of an alkaloid extract of Aspidosperma ramiflorum Muell. Arg. (Apocynaceae), against the extracellular forms promastigotes of L. (L.) amazonensis and L. (V.) braziliensis. The alkaloid extract of A. ramiflorum was much more effective against L. (L.) amazonensis (LD50 < 47 µg/ml) than L. (V.) braziliensis. Based on these in vitro results against L. (L.) amazonensis new studies should be made to find the compounds with anti-leishmanial activity.

Pharmacotherapy and analysis of gaseous mediators in hypertensive patients

OBJECTIVE To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. METHODS Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. RESULTS It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p<0.03) and the hydrogen sulphide concentration was significantly higher in hypertensive plasma in use of calcium channel antagonists (p<0.002). CONCLUSION The findings suggest that these medications have as additional action mechanism the improvement of endothelial dysfunction by elevate plasma levels of vasodilatory substances.

The fallacy of racial pharmacogenomics

Personalized pharmacogenomics aims to use individual genotypes to direct medical treatment. Unfortunately, the loci relevant for the pharmacokinetics and especially the pharmacodynamics of most drugs are still unknown. Moreover, we still do not understand the role that individual genotypes play in modulating the pathogenesis, the clinical course and the susceptibility to drugs of human diseases which, although appearing homogeneous on the surface, may vary from patient to patient. To try to deal with this situation, it has been proposed to use interpopulational variability as a reference for drug development and prescription, leading to the development of "race-targeted drugs". Given the present limitations of genomic knowledge and of the tools needed to fully implement it today, some investigators have proposed to use racial criteria as a palliative measure until personalized pharmacogenomics is fully developed. This was the rationale for the FDA approval of BiDil for treatment of heart failure in African Americans. I will evaluate the efficacy and safety of racial pharmacogenomics here and conclude that it fails on both counts. Next I shall review the perspectives and the predicted rate of development of clinical genomic studies. The conclusion is that "next-generation" genomic sequencing is advancing at a tremendous rate and that true personalized pharmacogenomics, based on individual genotyping, should soon become a clinical reality.

Access to continued-use medication among older adults, Brazil

OBJECTIVE To determine the prevalence and associated access factors for all continued-use prescription drugs and the ways in which they can be obtained.METHODS Data was obtained from the 2008 Household National Survey. The sample comprised 27,333 individuals above 60 years who reported that they used continued-use prescription drugs. A descriptive analysis and binary and multiple multinomial logistic regressions were performed.RESULTS 86.0% of the older adults had access to all the medication they needed, and among them, 50.7% purchased said medication. Those who obtained medication from the public health system were younger (60-64 years), did not have health insurance plans, and belonged to the lower income groups. It is remarkable that 14.0% of the subjects still had no access to any continued-use medication, and for those with more than four chronic diseases, this amount reached 22.0%. Those with a greater number of chronic diseases ran a higher risk of not having access to all the medication they needed.CONCLUSIONS There are some groups of older adults with an increased risk of not obtaining all the medication they need and of purchasing it. The results of this study are expected to contribute to guide programs and plans for access to medication in Brazil.

O tratamento específico como arma no controle da esquistossomose

The specific treatment of schistosomiasis has been though to prevent or revert severe forms of the disease, since 1957. Starting in 1977, prospective and controlled studies performed in different endemic areas of Brazil were able to confirm such facts. The new drugs, of high efficacy and well tolerated - Oxamniquine and Praziquantel - can actually prevent and cure the severe forms of some patients, contributing to change the morbidity pattern of the disease, thus being considered as important weapons in its control. Analysis of the Brazilian articles on the subject is presented.

Antimoniais empregados no tratamento da leishmaniose: estado da arte

Antimony preparations are the drugs of choice for the treatment of leishmaniasis over 90 years, a disease that currently affects 12 million people worldwide. Its introduction was based on 19th century concepts of therapeutic effects of metal salts as arsenicals and other metals, most of them abandoned due to toxic effects or better drugs. In the last three decades, there was a great improvement in the knowledge of cell biology and immunology of those infections, but chemotherapy has not been improved in the same strength. The structure and mechanism of action of the two pentavalent antimonial drugs of choice, meglumine antimoniate and sodium stibogluconate, are not well known and the contamination of those pharmaceutical by toxic contaminants have been verified.

ASSOCIATION BETWEEN SMOKING, CRACK COCAINE ABUSE AND THE DISCONTINUATION OF COMBINATION ANTIRETROVIRAL THERAPY IN RECIFE, PERNAMBUCO, BRAZIL

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.

Nurses' training on dealing with alcohol and drug abuse: a question of necessity

The purpose of this article is to present a brief review on the need for changes in nurses' undergraduate education concerning alcohol and drugs. Specialized literature makes it clear that nurses have difficulties giving care to psychoactive substance users as part of their functions in the various health care sites. This may be associated with a deficiency in formal education. In the face of the social importance concerning these related questions in the scope of research, care, and education, we made an attempt at deepening the study on this theme, which could contribute to changes in practice, care, and undergraduate nursing education.

Identity of care in a Psychosocial Care Center for Children and Adolescents who uses drugs

Objective To associate the territory of identity with the production of care within a PCC focusing on children and adolescents with drug abuse and their institutional identity. Method We used the “ process tracing methodology” in four research categories: focus groups, characterization of professionals, observing the everyday and interviewing two members of emblematic cases of the service. Results territory of identity of the institution, which operates the production of care is crossed by the difficulty of dealing with the complexity brought by the users and the performance of the PCC network. This paper is also permeated by different conceptions of care and small problematization of these issues in collective spaces of service. Conclusion The discussion in focus groups and other devices can be powerful resources to reframe the meaning of care and identity of collective service.

Use of psychoactive drugs and related falls among older people living in a community in Brazil

INTRODUCTION: Population aging in Brazil has increased the prevalence of neurodegenerative diseases (Parkinson's and Alzheimer's disease) and affective disorders (anxiety, depression), all common in old age. A retrospective study was carried out with the purpose of ascertaining if there is an association between falls and psychoactive medication use among older residents of a community in Brazil. METHODS: All residents aged 65+ (n=161) of one neighborhood of Campo Belo, Brazil (population of 48,000) were evaluated regarding the use of psychoactive drugs and the occurrence of falls in the 12 months preceding the study. Vision and hearing screenings were also performed. RESULTS: From the study population, 9.3% were taking prolonged half-life benzodiazepines, 4.4% anticonvulsants (mostly barbiturates), 2.5% antidepressants (all cyclics) and 8.1% alpha-methyldopa. No subject reported use of hypnotics, neuroleptics or drugs to treat Alzheimer's or Parkinson's diseases (except biperiden). As a whole, drugs that increase the risk of falls were used by 1/5 of this population. In the 12-month period preceding the study, 27 residents (16.8%) experienced falls and, of those, 4 (14.8%) had fracture(s). There was an independent association between psychoactive drug use and falls when variables such as age, gender, vision and hearing were controlled (p=0.02). CONCLUSIONS: Although the population of this neighborhood must be considered young (only 4% are 65 years old or more), there are already problems related to the use of psychoactive drugs among people. Prescribed anxiolytics, anticonvulsants, antidepressants and antihypertensives are not appropriate for this age group and their use is associated with falls.

Risk of drug interaction: combination of antidepressants and other drugs

OBJECTIVE: To assess the frequency of combination of antidepressants with other drugs and risk of drug interactions in the setting public hospital units in Brazil. METHODS: Prescriptions of all patients admitted to a public hospital from November 1996 to February 1997 were surveyed from the hospital's data processing center in São Paulo, Brazil. A manual search of case notes of all patients admitted to the psychiatric unit from January 1993 to December 1995 and all patients registered in the affective disorders outpatient clinic in December 1996 was carried out. Patients taking any antidepressant were identified and concomitant use of drugs was checked. By means of a software program (Micromedex®) drug interactions were identified. RESULTS: Out of 6,844 patients admitted to the hospital, 63 (0.9%) used antidepressants and 16 (25.3%) were at risk of drug interaction. Out of 311 patients in the psychiatric unit, 63 (20.2%) used antidepressants and 13 of them (20.6%) were at risk. Out of 87 patients in the affective disorders outpatient clinic, 43 (49.4%) took antidepressants and 7 (16.2%) were at risk. In general, the use of antidepressants was recorded in 169 patients and 36 (21.3%) were at risk of drug interactions. Twenty different forms of combinations at risk of drug interactions were identified: four were classified as mild, 15 moderate and one severe interaction. CONCLUSION: In the hospital general units the number of drug interactions per patient was higher than in the psychiatric unit; and prescription for depression was lower than expected.

Prevalence of alcohol abuse and associated factors in a population-based study

OBJECTIVE: To estimate the prevalence of alcohol abuse/dependence and identify associated factors among demographic, family, socioeconomic and mental health variables. METHODS: A household survey was carried out in the urban area of Campinas, southeastern Brazil, in 2003. A total of 515 subjects, aged 14 years or more were randomly selected using a stratified cluster sample. The Self-Report Questionnaire and the Alcohol Use Disorder Identification Test were used in the interview. Prevalences were calculated, and univariate and multivariate logistic analyses performed by estimating odds ratios and 95% confidence intervals. RESULTS: The estimated prevalence of alcohol abuse/dependence was 13.1% (95% CI: 8.4;19.9) in men and 4.1% (95% CI: 1.9;8.6) in women. In the final multiple logistic regression model, alcohol abuse/dependence was significantly associated with age, income, schooling, religion and illicit drug use. The adjusted odds ratios were significantly higher in following variables: income between 2,501 and 10,000 dollars (OR=10.29); income above 10,000 dollars (OR=10.20); less than 12 years of schooling (OR=13.42); no religion (OR=9.16) or religion other than Evangelical (OR=4.77); and illicit drug use during lifetime (OR=4.47). Alcohol abuse and dependence patterns were different according to age group. CONCLUSIONS: There is a significantly high prevalence of alcohol abuse/dependence in this population. The knowledge of factors associated with alcohol abuse, and differences in consumption patterns should be taken into account in the development of harm reduction strategies.