Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Knowledge translation in Uganda : a qualitative study of Ugandan midwives' and managers' perceived relevance of the sub-elements of the context cornerstone in the PARIHS framework

BACKGROUND: A large proportion of the annual 3.3 million neonatal deaths could be averted if there was a high uptake of basic evidence-based practices. In order to overcome this 'know-do' gap, there is an urgent need for in-depth understanding of knowledge translation (KT). A major factor to consider in the successful translation of knowledge into practice is the influence of organizational context. A theoretical framework highlighting this process is Promoting Action on Research Implementation in Health Services (PARIHS). However, research linked to this framework has almost exclusively been conducted in high-income countries. Therefore, the objective of this study was to examine the perceived relevance of the subelements of the organizational context cornerstone of the PARIHS framework, and also whether other factors in the organizational context were perceived to influence KT in a specific low-income setting. METHODS: This qualitative study was conducted in a district of Uganda, where focus group discussions and semi-structured interviews were conducted with midwives (n = 18) and managers (n = 5) within the catchment area of the general hospital. The interview guide was developed based on the context sub-elements in the PARIHS framework (receptive context, culture, leadership, and evaluation). Interviews were transcribed verbatim, followed by directed content analysis of the data. RESULTS: The sub-elements of organizational context in the PARIHS framework--i.e., receptive context, culture, leadership, and evaluation--also appear to be relevant in a low-income setting like Uganda, but there are additional factors to consider. Access to resources, commitment and informal payment, and community involvement were all perceived to play important roles for successful KT. CONCLUSIONS: In further development of the context assessment tool, assessing factors for successful implementation of evidence in low-income settings--resources, community involvement, and commitment and informal payment--should be considered for inclusion. For low-income settings, resources are of significant importance, and might be considered as a separate subelement of the PARIHS framework as a whole.

Process evaluation of a knowledge translation intervention using facilitation of local stakeholder groups to improve neonatal survival in the Quang Ninh province, Vietnam

BACKGROUND: Annually, 2.8 million neonatal deaths occur worldwide, despite the fact that three-quarters of them could be prevented if available evidence-based interventions were used. Facilitation of community groups has been recognized as a promising method to translate knowledge into practice. In northern Vietnam, the Neonatal Health - Knowledge Into Practice trial evaluated facilitation of community groups (2008-2011) and succeeded in reducing the neonatal mortality rate (adjusted odds ratio, 0.51; 95 % confidence interval 0.30-0.89). The aim of this paper is to report on the process (implementation and mechanism of impact) of this intervention. METHODS: Process data were excerpted from diary information from meetings with facilitators and intervention groups, and from supervisor records of monthly meetings with facilitators. Data were analyzed using descriptive statistics. An evaluation including attributes and skills of facilitators (e.g., group management, communication, and commitment) was performed at the end of the intervention using a six-item instrument. Odds ratios were analyzed, adjusted for cluster randomization using general linear mixed models. RESULTS: To ensure eight active facilitators over 3 years, 11 Women's Union representatives were recruited and trained. Of the 44 intervention groups, composed of health staff and commune stakeholders, 43 completed their activities until the end of the study. In total, 95 % (n = 1508) of the intended monthly meetings with an intervention group and a facilitator were conducted. The overall attendance of intervention group members was 86 %. The groups identified 32 unique problems and implemented 39 unique actions. The identified problems targeted health issues concerning both women and neonates. Actions implemented were mainly communication activities. Communes supported by a group with a facilitator who was rated high on attributes and skills (n = 27) had lower odds of neonatal mortality (odds ratio, 0.37; 95 % confidence interval, 0.19-0.73) than control communes (n = 46). CONCLUSIONS: This evaluation identified several factors that might have influenced the outcomes of the trial: continuity of intervention groups' work, adequate attributes and skills of facilitators, and targeting problems along a continuum of care. Such factors are important to consider in scaling-up efforts.

Degradação in situ da matéria seca e da fração fibrosa do capim marandu obtido por diferentes métodos de amostragem, no período seco do ano

Este trabalho foi realizado na Faculdade de Ciências Agrárias Veterinárias - Unesp - Jaboticabal e foi conduzido, com o objetivo de avaliar a influência do método de amostragem do pasto sobre a degradabilidade in situ da matéria seca e da fração fibrosa de capim Marandu, colhido no período seco dos anos de 2003 e 2005. O experimento foi instalado em delineamento de blocos casualizados com parcela subdividida, com três repetições, representadas pelos piquetes amostrados. Nas parcelas, foram avaliados cinco métodos de amostragens de forragem (método do quadrado metálico; método de avaliação através de extrusa de bovino da raça Nelore; método de avaliação por meio de extrusa de bovino Cruzado (Red Angus x Nelore); método de avaliação por meio do pastejo, simulando bovino da raça Nelore; método de avaliação por meio do pastejo, simulando bovino Cruzado (Red Angus x Nelore) e as subparcelas foram constituídas pelos anos de amostragem, 2003 e 2005. Foram determinadas as frações da cinética ruminal: solúvel A; insolúvel potencialmente degradável B; taxa de degradação Kd; degradação potencial (DP) e fração não degradável C da MS e degradação potencial (DP), fração não degradável C e taxa de degradação Kd da FDN e da FDA. de acordo com os resultados obtidos, observou-se que o método do quadrado metálico subestimou as características da degradação do capim. Os métodos do pastejo simulado se assemelharam muito ao das extrusas, no entanto, a prática do simulador é que assegurou a amostragem eficiente, conforme foi constatado pelos dados obtidos no ano de 2003 e 2005.

Health-related behavior and quality of life among the elderly: a population-based study

OBJETIVO: Analisar a associação de comportamentos saudáveis com a qualidade de vida relacionada à saúde em idosos. MÉTODOS: Estudo transversal de base populacional que envolveu 1.958 idosos residentes em quatro áreas do estado de São Paulo, em 2001/2002. A qualidade de vida foi aferida com o uso do instrumento Medical Outcomes Study SF-36-Item Short Form Health Survey. As oito escalas e os dois componentes do instrumento constituíram as variáveis dependentes e as independentes foram atividade física, freqüência semanal de ingestão de bebida alcoólica e hábito de fumar. Modelos de regressão linear múltipla foram usados para controlar o efeito de sexo, idade, escolaridade, trabalho, área de residência e número de doenças crônicas. RESULTADOS: Atividade física foi positivamente associada com as oito escalas do SF-36. As maiores associações foram encontradas em aspectos físicos (β = 11,9), capacidade funcional (β = 11,3) e no componente físico. Idosos que ingeriam bebida alcoólica pelo menos uma vez por semana apresentaram melhor qualidade de vida do que os que não ingeriam. Comparados com os que nunca fumaram, os fumantes tiveram pior qualidade de vida no componente mental (β = -2,4). CONCLUSÕES: Os resultados apresentam que praticar atividade física, consumir bebida alcoólica moderadamente e não fumar são fatores positivamente associados a uma melhor qualidade de vida em idosos.

Analysis of Ant Communities Comparing Two Methods for Sampling Ants in an Urban Park in the City of São Paulo, Brazil

This study aimed to analyze the species composition and functional groups of the ant community and to assess the efficiency of two sampling methods, pitfall and leaf litter sampling, in an urban park. A total of 1,401 ants were collected, which belonged to six subfamilies and 36 species. The predominant species was Wasmannia auropunctata (present in 45.36% of the samples), while the functional group of opportunistic ants were the most frequent (present in 83.75% of the samples) and abundant (95.29% of the total collected specimens) functional group. The Jaccard Similarity Index showed a low similarity between the two sampling methods, as the difference of the number of individuals for each species between these two methods was not significant in only one case (Linepithema sp. 1, p = 0.4561). The fungus-growing and cryptic ants were more collected in leaflitter samples (p<0.0001; p = 0.0348 respectively). Although there was no significant difference (p = 0.6397) between the two sampling methods for the total individuals of opportunistic ants, more species of this group were collected in pitfall traps. This difference was not significant because of the high presence of W. auropunctata, an opportunistic ant, in samples of leaf litter. Due to the predominance of tramp ants in the studied area, this article illustrates the importance of green urban areas in ant control strategies, since these sites could be used as a source of new colonization for these ants. Furthermore, the combination of the two sampling methods seems to be complementary for obtaining a more complete picture of the ant community.

Self-medication in children and adolescents

Objective: To determine the prevalence of self-medication in children and adolescents in the municipalities of Limeira and Piracicaba, state of S (a) over tildeo Paulo, and to correlate results with sociodemographic indicators and with the use of health care services (public or private).Methods: Descriptive population-based study of a simple random sample from the two municipalities, comprised of 772 inhabitants from 85 urban census sectors selected through cluster sampling. Inclusion criteria: age <= 18 years; interview with one parent/tutor; consumption of at least one drug in the previous 15 days. Subjects were divided into two study groups according to their pattern of drug use: self-medication (lay advice) and medical prescription. Linear association tests, descriptive analysis of variables and multiple logistic regression tests were carried out to analyze data.Results: the prevalence of self-medication was 56.6%. Mothers (51%) and drugstore employees (20.1%) were most frequently responsible for self-medication. The main groups of self-prescribed drugs were: analgesic/antipyretic and non-hormonal anti-inflammatory drugs (52.9%); drugs acting on the respiratory tract (15.4%) and gastrointestinal drugs (9.6%); and systemic antibiotics (8.6%). The situation that most commonly motivated self-medication were respiratory diseases (17.2%), fever (15%), and headache (14%). Subjects in the age group of 7-18 years (odds ratio = 2.81) and public health care users (odds ratio = 1.52) showed increased risk for self-medication.Conclusions: the prevalence of self-medication in children and adolescents was high, which reinforces the need for public health interventions aiming at preventing this practice.

A study on automatic methods based on mathematical morphology for Martian dust devil tracks detection

This paper presents three methods for automatic detection of dust devils tracks in images of Mars. The methods are mainly based on Mathematical Morphology and results of their performance are analyzed and compared. A dataset of 21 images from the surface of Mars representative of the diversity of those track features were considered for developing, testing and evaluating our methods, confronting their outputs with ground truth images made manually. Methods 1 and 3, based on closing top-hat and path closing top-hat, respectively, showed similar mean accuracies around 90% but the time of processing was much greater for method 1 than for method 3. Method 2, based on radial closing, was the fastest but showed worse mean accuracy. Thus, this was the tiebreak factor. © 2011 Springer-Verlag.

Integration of Genomics in Cancer Care

Purpose: The article aims to introduce nurses to how genetics-genomics is currently integrated into cancer care from prevention to treatment and influencing oncology nursing practice. Organizing Construct: An overview of genetics-genomics is described as it relates to cancer etiology, hereditary cancer syndromes, epigenetics factors, and management of care considerations. Methods: Peer-reviewed literature and expert professional guidelines were reviewed to address concepts of genetics-genomics in cancer care. Findings: Cancer is now known to be heterogeneous at the molecular level, with genetic and genomic factors underlying the etiology of all cancers. Understanding how these factors contribute to the development and treatment of both sporadic and hereditary cancers is important in cancer risk assessment, prevention, diagnosis, treatment, and long-term management and surveillance. Conclusions: Rapidly developing advances in genetics-genomics are changing all aspects of cancer care, with implications for nursing practice. Clinical Relevance: Nurses can educate cancer patients and their families about genetic-genomic advances and advocate for use of evidence-based genetic-genomic practice guidelines to reduce cancer risk and improve outcomes in cancer management. © 2013 Sigma Theta Tau International.

Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin

Background: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. Objective: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. Methods: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. Results: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. Conclusions: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice. © 2013 Elsevier Inc. All rights reserved.

Mapeamento das evidências das revisões sistemáticas do Grupo Anestesiologia da Colaboração Cochrane: entendendo seu valor para a prática clínica

Pós-graduação em Anestesiologia - FMB

Perioperative fluid therapy: a statement from the international fluid optimization group

Perioperative fluid therapy remains a highly debated topic. Its purpose is to maintain or restore effective circulating blood volume during the immediate perioperative period. Maintaining effective circulating blood volume and pressure are key components of assuring adequate organ perfusion while avoiding the risks associated with either organ hypo- or hyperperfusion. Relative to perioperative fluid therapy, three inescapable conclusions exist: overhydration is bad, underhydration is bad, and what we assume about the fluid status of our patients may be incorrect. There is wide variability of practice, both between individuals and institutions. The aims of this paper are to clearly define the risks and benefits of fluid choices within the perioperative space, to describe current evidence-based methodologies for their administration, and ultimately to reduce the variability with which perioperative fluids are administered. Based on the abovementioned acknowledgements, a group of 72 researchers, well known within the field of fluid resuscitation, were invited, via email, to attend a meeting that was held in Chicago in 2011 to discuss perioperative fluid therapy. From the 72 invitees, 14 researchers representing 7 countries attended, and thus, the international Fluid Optimization Group (FOG) came into existence. These researches, working collaboratively, have reviewed the data from 162 different fluid resuscitation papers including both operative and intensive care unit populations. This manuscript is the result of 3 years of evidence-based, discussions, analysis, and synthesis of the currently known risks and benefits of individual fluids and the best methods for administering them. The results of this review paper provide an overview of the components of an effective perioperative fluid administration plan and address both the physiologic principles and outcomes of fluid administration. We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive. This paper provides a general approach to fluid therapy and practical recommendations.

Estimating abundance of killer whales in the nearshore waters of the Gulf of Alaska and Aleutian Islands using line-transect sampling

Killer whale (Orcinus orca Linnaeus, 1758) abundance in the North Pacific is known only for a few populations for which extensive longitudinal data are available, with little quantitative data from more remote regions. Line-transect ship surveys were conducted in July and August of 2001–2003 in coastal waters of the western Gulf of Alaska and the Aleutian Islands. Conventional and Multiple Covariate Distance Sampling methods were used to estimate the abundance of different killer whale ecotypes, which were distinguished based upon morphological and genetic data. Abundance was calculated separately for two data sets that differed in the method by which killer whale group size data were obtained. Initial group size (IGS) data corresponded to estimates of group size at the time of first sighting, and post-encounter group size (PEGS) corresponded to estimates made after closely approaching sighted groups.

SAMPLING OF CORN TO ASSESS BIRD DAMAGE: A Preliminary Review of a Comprehensive Study

"How large a sample is needed to survey the bird damage to corn in a county in Ohio or New Jersey or South Dakota?" Like those in the Bureau of Sport Fisheries and Wildlife and the U.S.D.A. who have been faced with a question of this sort we found only meager information on which to base an answer, whether the problem related to a county in Ohio or to one in New Jersey, or elsewhere. Many sampling methods and rates of sampling did yield reliable estimates but the judgment was often intuitive or based on the reasonableness of the resulting data. Later, when planning the next study or survey, little additional information was available on whether 40 samples of 5 ears each or 5 samples of 200 ears should be examined, i.e., examination of a large number of small samples or a small number of large samples. What information is needed to make a reliable decision? Those of us involved with the Agricultural Experiment Station regional project concerned with the problems of bird damage to crops, known as NE-49, thought we might supply an ans¬wer if we had a corn field in which all the damage was measured. If all the damage were known, we could then sample this field in various ways and see how the estimates from these samplings compared to the actual damage and pin-point the best and most accurate sampling procedure. Eventually the investigators in four states became involved in this work1 and instead of one field we were able to broaden the geographical base by examining all the corn ears in 2 half-acre sections of fields in each state, 8 sections in all. When the corn had matured well past the dough stage, damage on each corn ear was assessed, without removing the ear from the stalk, by visually estimating the percent of the kernel surface which had been destroyed and rating it in one of 5 damage categories. Measurements (by row-centimeters) of the rows of kernels pecked by birds also were made on selected ears representing all categories and all parts of each field section. These measurements provided conversion factors that, when fed into a computer, were applied to the more than 72,000 visually assessed ears. The machine now had in its memory and could supply on demand a map showing each ear, its location and the intensity of the damage.

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.