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.

Pulmonary Surfactant in Respiratory Syncytial Virus Bronchiolitis: The Role in Pathogenesis and Clinical Implications

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of lower respiratory tract infection, and the most frequent reason for hospitalization among infants throughout the world. In addition to the acute consequences of the disease, RSV bronchiolitis in early childhood is related to further development of recurrent wheezing and asthma. Despite the medical and economic burden of the disease, therapeutic options are limited to supportive measures, and mechanical ventilation in severe cases. Growing evidence suggests an important role of changes in pulmonary surfactant content and composition in the pathogenesis of severe RSV bronchiolitis. Besides the well-known importance of pulmonary surfactant in maintenance of pulmonary homeostasis and lung mechanics, the surfactant proteins SP-A and SP-D are essential components of the pulmonary innate immune system. Deficiencies of such proteins, which develop in severe RSV bronchiolitis, may be related to impairment in viral clearance, and exacerbated inflammatory response. A comprehensive understanding of the role of the pulmonary surfactant in the pathogenesis of the disease may help the development of new treatment strategies. We conducted a review of the literature to analyze the evidences of pulmonary surfactant changes in the pathogenesis of severe RSV bronchiolitis, its relation to the inflammatory and immune response, and the possible role of pulmonary surfactant replacement in the treatment of the disease. Pediatr Pulmonol. 2011; 46:415-420. (c) 2010 Wiley-Liss, Inc.

Medical treatment and the good death: an ethical analysis of euthanasia, physician assisted suicide, and the right to die

Frequent advances in medical technologies have brought fonh many innovative treatments that allow medical teams to treal many patients with grave illness and serious trauma who would have died only a few years earlier. These changes have given some patients a second chance at life, but for others. these new treatments have merely prolonged their dying. Instead of dying relatively painlessly, these unfortunate patients often suffer from painful tenninal illnesses or exist in a comatose state that robs them of their dignity, since they cannot survive without advanced and often dehumanizing forms of treatment. Due to many of these concerns, euthanasia has become a central issue in medical ethics. Additionally, the debate is impacted by those who believe that patients have the right make choices about the method and timing of their deaths. Euthanasia is defined as a deliberate act by a physician to hasten the death of a patient, whether through active methods such as an injection of morphine, or through the withdrawal of advanced forms of medical care, for reasons of mercy because of a medical condition that they have. This study explores the question of whether euthanasia is an ethical practice and, as determined by ethical theories and professional codes of ethics, whether the physician is allowed to provide the means to give the patient a path to a "good death," rather than one filled with physical and mental suffering. The paper also asks if there is a relevant moral difference between the active and passive forms of euthanasia and seeks to define requirements to ensure fully voluntary decision making through an evaluation of the factors necessary to produce fully informed consent. Additionally, the proper treatments for patients who suffer from painful terminal illnesses, those who exist in persistent vegetative states and infants born with many diverse medical problems are examined. The ultimate conclusions that are reached in the paper are that euthanasia is an ethical practice in certain specific circumstances for patients who have a very low quality of life due to pain, illness or serious mental deficits as a result of irreversible coma, persistent vegetative state or end-stage clinical dementia. This is defended by the fact that the rights of the patient to determine his or her own fate and to autonomously decide the way that he or she dies are paramount to all other factors in decisions of life and death. There are also circumstances where decisions can be made by health care teams in conjunction with the family to hasten the deaths of incompetent patients when continued existence is clearly not in their best interest, as is the case of infants who are born with serious physical anomalies, who are either 'born dying' or have no prospect for a life that is of a reasonable quality. I have rejected the distinction between active and passive methods of euthanasia and have instead chosen to focus on the intentions of the treating physician and the voluntary nature of the patient's request. When applied in equivalent circumstances, active and passive methods of euthanasia produce the same effects, and if the choice to hasten the death of the patient is ethical, then the use of either method can be accepted. The use of active methods of euthanasia and active forms of withdrawal of life support, such as the removal of a respirator are both conscious decisions to end the life of the patient and both bring death within a short period of time. It is false to maintain a distinction that believes that one is active killing. whereas the other form only allows nature to take it's course. Both are conscious choices to hasten the patient's death and should be evaluated as such. Additionally, through an examination of the Hippocratic Oath, and statements made by the American Medical Association and the American College of physicians, it can be shown that the ideals that the medical profession maintains and the respect for the interests of the patient that it holds allows the physician to give aid to patients who wish to choose death as an alternative to continued suffering. The physician is also allowed to and in some circumstances, is morally required, to help dying patients whether through active or passive forms of euthanasia or through assisted suicide. Euthanasia is a difficult topic to think about, but in the end, we should support the choice that respects the patient's autonomous choice or clear best interest and the respect that we have for their dignity and personal worth.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

CONTEXTO E OBJETIVO: Urticária-angioedema crônico é enfermidade freqüente, complexa e multicausal. O objetivo foi estudar as características sociodemográficas, clínicas, os fatores causais, agravantes e a evolução da enfermidade. TIPO DE ESTUDO E LOCAL: Descritivo e prospectivo, realizado no ambulatório de Dermatologia da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). MÉTODOS: Foram avaliados pacientes com diagnóstico de urticária-angioedema crônico através de dados sociodemográficos, anamnese, exames dermatológico, clínico e laboratorial, com ênfase nos fatores causais, agravantes e na evolução da enfermidade. RESULTADOS: 125 pacientes foram incluídos, 95 mulheres e 30 homens. Predominaram mulheres de 30 a 40 anos e homens de 10 a 20 anos. A idade média foi de 35 anos para as mulheres e 32 anos para os homens. Predominaram pacientes de raça branca, residentes em zona urbana e casados. O tempo médio de doença foi de 45,6 meses e de cada lesão foi de 5,6 horas. A metade dos casos tinha surtos diariamente e associação de urticária com angioedema. Não houve horário preferencial de aparecimento dos surtos, mas o noturno foi o horário de piora mais citado. A causa foi esclarecida em 37,6%, predominando as infecções. O estresse foi o agravante mais referido. O tempo médio de acompanhamento foi de 11,7 meses e 60% evoluíram para o controle, 32% melhoraram, 9% mantiveram-se inalterados e um caso piorou. CONCLUSÕES: Urticária-angioedema ocorreu mais em mulheres de meia-idade. A causa foi esclarecida em um terço dos pacientes e metade deles teve controle da doença em aproximadamente um ano.

Medical conditions and body pain in patients presenting orofacial pain

OBJETIVO: Verificar a frequência de problemas médicos autorrelatados e a frequência de áreas de dor no corpo em pacientes com dor orofacial, comparando-os a pacientes submetidos a tratamento odontológico de rotina. MÉTODOS: Os dados foram coletados dos arquivos da Clínica de Dor Orofacial (Grupo A, n=319) e de clínicas de tratamento odontológico rotineiro (Grupo B, n=84) da Faculdade de Odontologia de Araraquara, São Paulo, Brasil. Os indivíduos responderam a questionários e preencheram um mapa corporal indicando os locais de dor. RESULTADOS: O teste de Mann-Whitney demonstrou que o Grupo A apresentou uma média de relatos de problemas médicos superior ao Grupo B (p=0,004). Para ambos os grupos, o teste de correlação de Pearson demonstrou correlação positiva entre os problemas médicos e a frequência de áreas dolorosas (respectivamente, 0,478, p=0,001 e 0,246, p=0,000). CONCLUSÕES: O Grupo A relatou maior número de problemas médicos e houve correlação positiva entre a frequência desses problemas e a de áreas de dor para ambos os grupos.

Candidemia in a Brazilian tertiary hospital: microbiological and clinical features over a six-year period

Yeasts are becoming a common cause of nosocomial fungal infections in immunocompromised patients. Such infections often develop into sepsis with high mortality rates. The aim of this study was to evaluate some of the numerous factors associated with the development of candidemia. Medical records were retrospectively analyzed of 98 Candida spp. patients. Results showed that the most prevalent risk factors for developing candidemia were: antibiotics and antifungal agents (93.9% and 79.6%, respectively); the use of central venous catheter (93.9%); mechanical ventilation (73.5%); and parenteral nutrition (60.2%). The main species of Candida found were: C. parapsilosis (37.76%), C. albicans (33.67%); and others (28.57%). C. glabrata showed the highest mortality rate (75%), followed by C. tropicalis (57.1%) and C. albicans (54.5%). The elevated mortality rate found in this study indicates that preventive measures against candidemia must be emphasized in hospitals.

The Xmnl polymorphic site 5 ' to the gene G gamma in a Brazilian patient with sickle cell anaemia - fetal haemoglobin concentration, haematology and clinical features

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Hematological, hepatic, and renal evaluation in Aotus azarai infulatus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Antenatal corticosteroid use and clinical evolution of preterm newborn infants

Objectives: To describe the use of antenatal corticosteroid and clinical evolution of preterm babies. Methods: An observational prospective cohort study was carried out. All 463 pregnant women and their 514 newborn babies with gestational age ranging from 23 to 34 weeks, born at the Brazilian Neonatal Research Network units, were evaluated from August 1 to December 31, 2001. The data were obtained through maternal interview, analysis of medical records, and follow-up of the newborn infants. Data analysis was performed with the use of chi-square, t Student, Mann-Whitney, and ANOVA tests and multiple logistic regression, with level of significance set at 5%. Results: Treatment was directly associated with the number of prenatal visits, with maternal hypertension and with the antenatal use of tocolytic agents. Babies from treated pregnant women presented better Apgar scores at the 1st and 5th minute, reduced need for intervention in the delivery room and lower SNAPPE II. They were born with higher birth weight, longer gestational age and needed less surfactant use, ventilation, and oxygenation time. After multiple logistic regression, the use of antenatal corticosteroid independently improved birth conditions, decreased ventilation time, being related to increased occurrence of neonatal sepsis. Conclusions: The use of corticosteroid was associated with better prenatal care and birth conditions, better preterm evolution but higher risk of infection. Copyright © 2004 by Sociedade Brasileira de Pediatria.

Acquisition of suture skills during medical graduation by instructor-directed training: A randomized controlled study comparing senior medical students and faculty surgeons

Due to shortage of time and limited availability of faculty surgeons to teach basic surgical skills during medical graduation, the search for alternative ways of simulated training with feedback is needed. The purpose of this study was to compare the simulated teaching of suture skills to novice medical students by senior medical students and by experienced faculty surgeons. Forty-eight novice medical students were randomly assigned to three practice conditions on bench model (n = 16): self-directed suture training (control), senior medical student-directed suture skills' training, or experienced faculty surgeon-directed suture skills' training. Pre- and post-tests were applied. Global Rating Scale with blinded evaluation and self-perceived confidence based on Likert scale were used to assess all suture performances in pre- and post-training. Effect size was also calculated. The analysis made after training showed that the students who received feedback from the instructors had better performance based on the Global Rating Scale (all p < 0.0000) and felt more confident to carry out sutures (all p < 0.0000) when compared to the control. There was no significant difference (all p > 0.05) between the student-directed teaching and faculty-directed teaching groups. The magnitude of the effect (instructor-directed training suture) was considered large (>0.80) in all measurements. The acquisition of suture skills after student-directed training was similar to the training supervised by faculty surgeon, and the increase in suture performances of trainees that received instructor administered training was superior to self-directed learning. © 2013 Springer-Verlag Italia.

Paracoccidioides lutzii sp nov.: biological and clinical implications

Paracoccidioides lutzii, formerly known as 'Pb01-like' strains in the P. brasiliensis complex, is proposed as a new species based on phylogenetic and comparative genomics data, recombination analysis, and morphological characteristics. Conidia of P. lutzii are elongated, different from those of P. brasiliensis. P. lutzii occurs in the central and northern regions of Brazil. Studies comparing P. brasiliensis and P. lutzii may have significant clinical consequences for the diagnosis and treatment of paracoccidioidomycosis.

Painful procedures and analgesia in the NICU: what has changed in the medical perception and practice in a ten-year period?

To compare the use of analgesia versus neonatologists' perception regarding analgesic use in painful procedures in the years 2001, 2006, and 2011. This was a prospective cohort study of all newborns admitted to four university neonatal intensive care units (NICUs) during one month in 2001, 2006, and 2011. The frequency of analgesic prescription for painful procedures was evaluated. Of the 202 neonatologists, 188 answered a questionnaire giving their opinion on the intensity of pain during lumbar puncture (LP), tracheal intubation, mechanical ventilation (MV), and postoperative period (PO) using a 10-cm visual analogic scale (VAS; pain >3cm). For LP, 12% (2001), 43% (2006), and 36% (2011) were performed using analgesia. Among the neonatologists, 40-50% reported VAS >3 for LP in all study periods. For intubation, 30% received analgesia in the study periods, and 35% (2001), 55% (2006), and 73% (2011) of the neonatologists reported VAS >3 and would prescribe analgesia for this procedure. As for MV, 45% (2001), 64% (2006), and 48% (2011) of patient-days were under analgesia; 56% (2001), 57% (2006), and 26% (2011) of neonatologists reported VAS >3 and said they would use analgesia during MV. For the first three PO days, 37% (2001), 78% (2006), and 89% (2011) of the patients received analgesia and more than 90% of neonatologists reported VAS >3 for major surgeries. Despite an increase in the medical perception of neonatal pain and in analgesic use during painful procedures, the gap between clinical practice and neonatologist perception of analgesia need did not change during the ten-year period.

Epidemiological and clinical characteristics of injuries among adolescents attended at an emergency service in the city of Ribeirao Preto, Sao Paulo

CONTEXT AND OBJECTIVE: Injuries are an important cause of morbidity during adolescence, but can be avoided through learning about some of their characteristics. This study aimed to identify the most frequent injuries among adolescents attended at an emergency service. DESIGN AND SETTING: Retrospective descriptive study on adolescents attended at the emergency service of the Teaching Health Center, Faculdade de Medicina de Ribeirao Preto (FMRP), between January 1, 2009, and September 30, 2009. METHODS: Age, sex, type of injury, site, day and time of occurrence, part of body involved, care received, whether the adolescent was accompanied at the time of injury and whether any type of counseling regarding injury prevention had been given were analyzed. RESULTS: Among 180 adolescents attended, 106 (58.8%) were boys and 74 (41.1%) were girls. Their ages were: 10 to 12 (66/36.6%), 12 to 14 (60/33.3%) and 14 to 16 years (54/30%). The injuries had occurred in public places (47.7%) and at home (21.1%). The main types were bruises (45.1%) and falls (39.2%), involving upper limbs (46.1%), lower limbs (31%) and head/neck (13.1%). The injuries occurred in the afternoon (44.4%) and morning (30%), on Mondays (17.7%) and Thursdays (16.6%). Radiological examinations were performed on 53.8%. At the time of injury, 76.1% of the adolescents were accompanied. Some type of counseling about injury prevention had been received by 39.4%. CONCLUSIONS: Although the injuries were of low severity, preventive attitudes need to be incorporated in order to reduce the risks and provide greater safety for adolescents.

Hematology and Serum Chemistry of Free-ranging Jaguars (Panthera onca)

We collected and analyzed blood samples from 12 free-ranging jaguars (Panthera onca). Clinical examinations, hematolog, and serum chemistry indicate the jaguars were in good overall health. Results may help as values for free-ranging jaguars under the same handling conditions.