The viewpoint of health professionals on the role of basic units in the healthcare network of the Brazilian Unified Health System

In the process of creation of the Unified Health System (SUS) as a universal policy seeking to ensure comprehensive care, unscheduled assistance in primary healthcare units (UBS) is an unresolved challenge. The scope of this paper is to analyze the viewpoint of health professionals on the role of primary healthcare units in meeting this demand. It is a transversal study of qualitative data obtained through questionnaires and interviews with 106 medical practitioners from 6 emergency medical services and 190 professionals from 30 units. They explained why people seek emergency care for occurrences pertaining to primary care. The content analysis technique with thematic categories was used for data analysis. Lack of resources and problems with primary health unit work processes (50.8%) were the reasons most frequently cited by emergency care physicians to explain this inadequate demand. Only 33.3% of the health unit professionals agreed that these occurrences should be attended in the primary healthcare services. The limited viewpoint of the role of health services on the unscheduled care, particularly among primary care professionals, possibly leads to restrictive practices for access by the population.

The implementation of the Medical Regulation Office and Mobile Emergency Attendance System and its impact on the gravity profile of non-traumatic afflictions treated in a University Hospital: a research study

Abstract Background The public health system of Brazil is structured by a network of increasing complexity, but the low resolution of emergency care at pre-hospital units and the lack of organization of patient flow overloaded the hospitals, mainly the ones of higher complexity. The knowledge of this phenomenon induced Ribeirão Preto to implement the Medical Regulation Office and the Mobile Emergency Attendance System. The objective of this study was to analyze the impact of these services on the gravity profile of non-traumatic afflictions in a University Hospital. Methods The study conducted a retrospective analysis of the medical records of 906 patients older than 13 years of age who entered the Emergency Care Unit of the Hospital of the University of São Paulo School of Medicine at Ribeirão Preto. All presented acute non-traumatic afflictions and were admitted to the Internal Medicine, Surgery or Neurology Departments during two study periods: May 1996 (prior to) and May 2001 (after the implementation of the Medical Regulation Office and Mobile Emergency Attendance System). Demographics and mortality risk levels calculated by Acute Physiology and Chronic Health Evaluation II (APACHE II) were determined. Results From 1996 to 2001, the mean age increased from 49 ± 0.9 to 52 ± 0.9 (P = 0.021), as did the percentage of co-morbidities, from 66.6 to 77.0 (P = 0.0001), the number of in-hospital complications from 260 to 284 (P = 0.0001), the mean calculated APACHE II mortality risk increased from 12.0 ± 0.5 to 14.8 ± 0.6 (P = 0.0008) and mortality rate from 6.1 to 12.2 (P = 0.002). The differences were more significant for patients admitted to the Internal Medicine Department. Conclusion The implementation of the Medical Regulation and Mobile Emergency Attendance System contributed to directing patients with higher gravity scores to the Emergency Care Unit, demonstrating the potential of these services for hierarchical structuring of pre-hospital networks and referrals.

The standpoint of professionals on the presence and demands of men on the healthcare services: perspectives for the analysis of the implementation of the Comprehensive Healthcare Policy for Men

In 2009, the Brazilian Comprehensive Healthcare Policy for Men (PNAISH) was launched in Brazil, seeking to reduce morbidity and mortality in this population group. This article strives to analyze the conceptions that health professionals have about the specific demands and behaviors of the male population served by the healthcare services. The data analyzed are part of a larger research project, the objective of which was to evaluate the initial actions of the implementation of PNAISH. Ethnographic observations in 11 health services and semi-structured interviews were conducted with 21 health professionals. From the perspective of health professionals, the presence of men in the healthcare services is still limited. According to them, it is comprised of two types of clients: workers and the elderly. The male behavior characteristics - haste, objectivity, fear and resistance - and the difficulty faced by health services in receiving this population are the main factors that drive men away from health services. Although the concept of gender is central to PNAISH, it is only triggered by healthcare professionals in order to justify the social standards expected in terms of men's behavior. The attribution of men's behavior to cultural factors ultimately obscures the relations of power that underlie gender relations.

Therapeutic Project at Extra-Hospital Mental Health Services: a critical reflection on the elaboration and management of services' therapeutic projects

Based on a study conducted in Ribeirao Preto, SP, Brazil in extra-hospital mental health services that addressed the organization of these services, therapeutic projects and the inclusion of psychosocial rehabilitation in health actions available, a theoretical-critical reflection concerning the development process of the therapeutic projects by the services' teams is presented. The qualitative study was conducted in an outpatient clinic and a Psychosocial Care Center. Data were collected through semi-structured interviews and focal groups. Data analysis was based on the hermeneutic dialectic philosophy of Jurgen Habermas according to the techniques of reconstruction and interpretation. Data analysis revealed that professionals have difficulty developing and managing therapeutic projects. Health actions are made available without being concretely supported by a proposal guiding the service's practical activities. The therapeutic projects are referred by professionals as the result of guidelines provided by management levels or technical orientations inherent to each profession but not as an activity that represents a philosophy of work of the health team. When the therapeutic project is focused on as a type of consensus that results from a communicative action directed to a mutual and intersubjective understanding among the members of the mental health extra-hospital team, the difficulties of the services' team dialogically organizing themselves to collectively construct the therapeutic project is evidenced.

Accidents by external causes in adolescents: care in sentinel urgency and emergency services in the Brazilian State Capitals-2009

Adolescents are seeking new references and experiences, which may involve attitudes of risk and exposure to accidents and violence from external causes. These events constitute a serious Public Health problem. The scope of this study was to analyze the occurrence of accidents by external causes in adolescents from 10 to 19 years of age attended at sentinel urgency and emergency services in Brazil. Data from the 2009 Surveillance System for Violence and Accidents (VIVA 2009) was analyzed in 74 emergency units in 23 state capitals and the Federal District. The findings revealed that 6,434 adolescents (89.8%) were victims of accidents and 730 (10.2 %) were victims of violence. The main causes of the accidents were falls and traffic accidents, and assaults were predominant in violence. For both accidents and violence, non-white male adolescents were predominant and the events occurred most frequently on the public highways. A marked increase was detected, with hospitalization of victims of violence between 15 and 19 years of age. Understanding the epidemiological reality of external causes among adolescents represents an important tool for health prevention and promotion policies and the culture of peace seeking to reduce morbidity and mortality.

Lethal effects of abamectin on the aquatic organisms Daphnia similis, Chironomus xanthus and Danio rerio

Abamectin is used as an acaricide and insecticide for fruits, vegetables and ornamental plants, as well as a parasiticide for animals. One of the major problems of applying pesticides to crops is the likelihood of contaminating aquatic ecosystems by drift or runoff. Therefore, toxicity tests in the laboratory are important tools to predict the effects of chemical substances in aquatic ecosystems. The aim of this study was to assess the potential hazards of abamectin to the freshwater biota and consequently the possible losses of ecological services in contaminated water bodies. For this purpose, we identified the toxicity of abamectin on daphnids, insects and fish. Abamectin was highly toxic, with an EC50 48 h for Daphnia similis of 5.1 ng L-1, LC50 96 h for Chironomus xanthus of 2.67 mu g L-1 and LC50 48 h for Danio rerio of 33 mu g L-1. (C) 2011 Elsevier Ltd. All rights reserved.

The impact of late diagnosis on the survival of patients following their first AIDS-related hospitalization in Belo Horizonte, Brazil

The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and >= 1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity off acilitating HIV diagnosis.

Delay in the search for health services for the diagnosis of tuberculosis in Ribeirao Preto, Sao Paulo

The scope of this paper is to analyze delays in locating health services for the diagnosis of tuberculosis in Ribeirao Preto in 2009. An epidemiological and cross-sectional study was conducted with 94 TB patients undergoing treatment. A structured questionnaire, based on the Primary Care Assessment Tool adapted for TB care was used. A median (15 days or more) was established to characterize delay in health attendance. Using the Prevalence Ratio, the variables associated with longer delay were identified. The first healthcare services sought were the Emergency Services (ES) (57.5%). The longest period between seeking assistance occurred among males, aged between 50 and 59, who earned less than five minimum wages, had pulmonary TB, were new cases, were not co-infected with TB/HIV, did not consume alcohol, had satisfactory knowledge about TB before diagnosis (with a statistically significant association with delay) and who did not seek healthcare close to home before developing TB. There is a perceived need for training healthcare professionals about the signs and symptoms of the disease, reducing barriers of access to timely diagnosis of TB and widely disseminating it to the community in general.

Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians

The impact of biogeographical ancestry, self-reported 'race/color' and geographical origin on the frequency distribution of 10 CYP2C functional polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17) and their haplotypes was assessed in a representative cohort of the Brazilian population (n = 1034). TaqMan assays were used for allele discrimination at each CYP2C locus investigated. Individual proportions of European, African and Amerindian biogeographical ancestry were estimated using a panel of insertion-deletion polymorphisms. Multinomial log-linear models were applied to infer the statistical association between the CYP2C alleles and haplotypes (response variables), and biogeographical ancestry, self-reported Color and geographical origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from 3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were identified: block 1 consists of three single nucleotide polymorphisms (SNPs) (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11, CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis generated 41 haplotypes, of which eight had frequencies greater than 1% and together accounted for 96.4% of the overall genetic diversity. The distribution of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was significantly associated with self-reported Color and with the individual proportions of European and African genetic ancestry, irrespective of Color self-identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied continuously as the proportion of European ancestry increased. Collectively, these data strongly suggest that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies of the CYP2C cluster in order to avoid spurious conclusions based on improper matching of study cohorts. This conclusion extends to other polymorphic pharmacogenes among Brazilians, and most likely to other admixed populations of the Americas. The Pharmacogenomics Journal (2012) 12, 267-276; doi: 10.1038/tpj.2010.89; published online 21 December 2010

Opposing Roles for Cannabinoid Receptor Type-1 (CB1) and Transient Receptor Potential Vanilloid Type-1 Channel (TRPV1) on the Modulation of Panic-Like Responses in Rats

The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety-and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB1 and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB1-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB1-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB1 and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB1 receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders. Neuropsychopharmacology (2012) 37, 478-486; doi:10.1038/npp.2011.207; published online 21 September 2011

Effect of Type 2 Diabetes Mellitus on the Pharmacokinetics of Metformin in Obese Pregnant Women

Background and Objective The use of metformin throughout gestation by women with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) significantly reduces the number of first-trimester spontaneous abortions and the rate of occurrence of gestational diabetes and hypertensive syndromes. Metformin is taken up into renal tubular cells by organic cation transport 2 (OCT2) and eliminated unchanged into the urine. The objective of this study was to analyse the influence of T2DM on the pharmacokinetics of metformin in obese pregnant women and in a control group of non-diabetic obese pregnant women with PCOS. Methods Eight non-diabetic obese pregnant women with PCOS and nine obese pregnant women with T2DM taking oral metformin 850 mg every 12 h were evaluated throughout gestation. Serial blood samples were collected over a 12-h period during the third trimester of pregnancy. Steady-state plasma concentrations of metformin were determined by high-performance liquid chromatography with a UV detector. The pharmacokinetic results of the two groups, reported as median and 25th and 75th percentile, were compared statistically using the Mann Whitney test, with the level of significance set at p < 0.05. Results The pharmacokinetic parameters detected for PCOS versus T2DM patients, reported as median, were, respectively: elimination half-life 3.75 versus 4.00 h; time to maximum concentration 2.00 versus 3.00 h; maximum concentration 1.42 versus 1.21 mu g/mL; mean concentration 0.53 versus 0.56 mu g/mL; area under the plasma concentration time curve from time zero to 12 h 6.42 versus 6.73 mu g.h/mL; apparent total oral clearance 105.39 versus 98.38 L/h; apparent volume of distribution after oral administration 550.51 versus 490.98 L; and fluctuation (maximum minimum concentration variation) of 179.56 versus 181.73%. No significant differences in pharmacokinetic parameters were observed between the groups. Conclusion T2DM in the presence of insulin use does not influence the pharmacokinetics of metformin in pregnant patients, demonstrating the absence of a need to increase the dose, and consequently does not influence the OCT2-mediated transport in pregnant women with PCOS.

Influence of Genomic Ancestry on the Distribution of SLCO1B1, SLCO1B3 and ABCB1 Gene Polymorphisms among Brazilians

The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations.

Crotamine Pharmacology Revisited: Novel Insights Based on the Inhibition of K-V Channels

Crotamine, a 5-kDa peptide, possesses a unique biological versatility. Not only has its cell-penetrating activity become of clinical interest but, moreover, its potential selective antitumor activity is of great pharmacological importance. In the past, several studies have attempted to elucidate the exact molecular target responsible for the crotamine-induced skeletal muscle spasm. The aim of this study was to investigate whether crotamine affects voltage-gated potassium (K-V) channels in an effort to explain its in vivo effects. Crotamine was studied on ion channel function using the two-electrode voltage clamp technique on 16 cloned ion channels (12 K-V channels and 4 Na-V channels), expressed in Xenopus laevis oocytes. Crotamine selectively inhibits K-V 1.1, K-V 1.2, and K-V 1.3 channels with an IC50 of similar to 300 nM, and the key amino acids responsible for this molecular interaction are suggested. Our results demonstrate for the first time that the symptoms, which are observed in the typical crotamine syndrome, may result from the inhibition of K-V channels. The ability of crotamine to inhibit the potassium current through K-V channels unravels it as the first snake peptide with the unique multifunctionality of cell-penetrating and antitumoral activity combined with K-V channel-inhibiting properties. This new property of crotamine might explain some experimental observations and opens new perspectives on pharmacological uses.

Evidence-Based Information on the Clinical Use of Neurofeedback for ADHD

Neurofeedback (NF) is a training to enhance self-regulatory capacity over brain activity patterns and consequently over brain mental states. Recent findings suggest that NF is a promising alternative for the treatment of attention-deficit/hyperactivity disorder (ADHD). We comprehensively reviewed literature searching for studies on the effectiveness and specificity of NF for the treatment of ADHD. In addition, clinically informative evidence-based data are discussed. We found 3 systematic review on the use of NF for ADHD and 6 randomized controlled trials that have not been included in these reviews. Most nonrandomized controlled trials found positive results with medium-to-large effect sizes, but the evidence for effectiveness are less robust when only randomized controlled studies are considered. The direct comparison of NF and sham-NF in 3 published studies have found no group differences, nevertheless methodological caveats, such as the quality of the training protocol used, sample size, and sample selection may have contributed to the negative results. Further data on specificity comes from electrophysiological studies reporting that NF effectively changes brain activity patterns. No safety issues have emerged from clinical trials and NF seems to be well tolerated and accepted. Follow-up studies support long-term effects of NF. Currently there is no available data to guide clinicians on the predictors of response to NF and on optimal treatment protocol. In conclusion, NF is a valid option for the treatment for ADHD, but further evidence is required to guide its use.

Development of a recombinant fusion protein based on the dynein light chain LC8 for non-viral gene delivery

The low efficiency of gene transfer is a recurrent problem in DNA vaccine development and gene therapy studies using non-viral vectors such as plasmid DNA (pDNA). This is mainly due to the fact that during their traffic to the target cell's nuclei, plasmid vectors must overcome a series of physical, enzymatic and diffusional barriers. The main objective of this work is the development of recombinant proteins specifically designed for pDNA delivery, which take advantage of molecular motors like dynein, for the transport of cargos from the periphery to the centrosome of mammalian cells. A DNA binding sequence was fused to the N-terminus of the recombinant human dynein light chain LC8. Expression studies indicated that the fusion protein was correctly expressed in soluble form using E. coli BL21(DE3) strain. As expected, gel permeation assays found the purified protein mainly present as dimers, the functional oligomeric state of LC8. Gel retardation assays and atomic force microscopy proved the ability of the fusion protein to interact and condense pDNA. Zeta potential measurements indicated that LC8 with DNA binding domain (LD4) has an enhanced capacity to interact and condense pDNA, generating positively charged complexes. Transfection of cultured HeLa cells confirmed the ability of the LD4 to facilitate pDNA uptake and indicate the involvement of the retrograde transport in the intracellular trafficking of pDNA: LD4 complexes. Finally, cytotoxicity studies demonstrated a very low toxicity of the fusion protein vector, indicating the potential for in vivo applications. The study presented here is part of an effort to develop new modular shuttle proteins able to take advantage of strategies used by viruses to infect mammalian cells, aiming to provide new tools for gene therapy and DNA vaccination studies. (C) 2012 Elsevier B.V. All rights reserved.