Growth Factor Proteins and Treatment-Resistant Depression: A Place on the Path to Precision

Background: Since the neurotrophic hypothesis of depression was formulated, conflicting results have been reported regarding the role of growth factor proteins in depressed patients, including whether there are state or trait alterations found in patients compared to controls and whether they represent predictors of treatment response. Recently it has been hypothesized that heterogeneity of findings within this literature might be partly explained by participants' history of treatment-resistant depression. This study aimed to investigate the role of growth factor proteins in patients with treatment-resistant depression (TRD) undergoing an inpatient intervention.Methods: Blood samples were collected from 36 patients with TRD and 36 matched controls. Patients were assessed both at admission and discharge from a specialist inpatient program. We examined serum biomarker differences between patients and non-depressed matched controls, longitudinal changes after inpatient treatment and relationship to clinical outcomes. Additionally, the influence of potential covariates on biomarker levels were assessed.Results: Patients displayed lower serum levels of brain-derived neurotrophic factor (OR = 0.025; 95% CI = 0.001, 0.500) and vascular endothelial growth factor-C (VEGFC; OR = 0.083, 95% CI = 0.008, 0.839) as well as higher angiopoietin-1 receptor (Tie2; OR = 2.651, 95% CI = 1.325, 5.303) compared to controls. Patients were stratified into responders (56%) and non-responders (44%). Lower VEGFD levels at admission predicted subsequent non-response (OR = 4.817, 95% CI = 1.247, 11.674). During treatment, non-responders showed a decrease in VEGF and VEGFC levels, while responders showed no significant changes.Conclusion: TRD patients demonstrate a deficit of peripheral growth factors and our results suggest that markers of the VEGF family might decline over time in chronically depressed patients in spite of multidisciplinary treatment. The action of angiogenic proteins may play an important role in the pathophysiology of TRD, and pending comprehensive investigation may provide important insights for the future of precision psychiatry

Associations between Hemodialysis Facility Practices to Manage Fluid Volume and Intradialytic Hypotension and Patient Outcomes.

BACKGROUND AND OBJECTIVES Fluid overload and intradialytic hypotension are associated with cardiovascular events and mortality in patients on hemodialysis. We investigated associations between hemodialysis facility practices related to fluid volume and intradialytic hypotension and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data were analyzed from 10,250 patients in 273 facilities across 12 countries, from phase 4 of the Dialysis Outcomes and Practice Patterns Study (DOPPS; 2009-2012). Cox regression models (shared frailty) were used to estimate associations between facility practices reported by medical directors in response to the DOPPS Medical Directors Survey and all-cause and cardiovascular mortality and hospitalization, and cardiovascular events, adjusting for country, age, sex, dialysis vintage, predialysis systolic BP, cardiovascular comorbidities, diabetes, body mass index, smoking, residual kidney function, dialysis adequacy, and vascular access type. RESULTS Of ten facility practices tested (chosen ), having a protocol that specifies how often to assess dry weight in most patients was associated with lower all-cause (hazard ratio [HR], 0.78; 99% confidence interval [99% CI], 0.64 to 0.94) and cardiovascular mortality (HR, 0.72; 99% CI, 0.55 to 0.95). Routine orthostatic BP measurement to assess dry weight was associated with lower all-cause hospitalization (HR, 0.86; 99% CI, 0.77 to 0.97) and cardiovascular events (HR, 0.85; 99% CI, 0.73 to 0.98). Routine use of lower dialysate temperature to limit or prevent intradialytic hypotension was associated with lower cardiovascular mortality (HR, 0.76; 99% CI, 0.58 to 0.98). Routine use of an online volume indicator to assess dry weight was associated with higher all-cause hospitalization (HR, 1.19; 99% CI, 1.02 to 1.38). Routine use of sodium modeling/profiling to limit or prevent intradialytic hypotension was associated with higher all-cause mortality (HR, 1.36; 99% CI, 1.14 to 1.63), cardiovascular mortality (HR, 1.34; 99% CI, 1.04 to 1.73), and cardiovascular events (HR, 1.21; 99% CI, 1.03 to 1.43). CONCLUSIONS Hemodialysis facility practices relating to the management of fluid volume and intradialytic hypotension are associated with patient outcomes

Screening for Hepatitis B in partners and children of women positive for surface antigen, Burkina Faso

International audienceObjective To evaluate the implementation of a screening strategy for the partners and children of pregnant women with hepatitis B virus(HBV) attending antenatal care.Methods We identified pregnant women positive for HBV surface antigen (HBsAg) at antenatal consultation in Ouagadougou, Burkina Faso.At post-test counselling, women were advised to disclose their HBV status to partners and to encourage their partner and children to bescreened for HBsAg. We used multivariable logistic regression to explore factors associated with uptake of screening and HBsAg positivityamong family members.Findings Of 1000 HBsAg-positive women, 436/1000 partners and 215/1281 children were screened. HBsAg was detected in 55 (12.6%)partners and 24 (11.2%) children. After adjusting for confounders, uptake of screening was higher in partners who were married, whoattended the woman’s first post-test consultation and to whom the woman had disclosed her HBV status. In children, HBsAg positivity wasassociated with being born before the introduction of infant hepatitis B vaccination in Burkina Faso (not significant in the multivariableanalysis), having a mother positive for HBV e-antigen (adjusted OR: 8.57; 95% CI: 2.49–29.48) or having a mother with HBV DNA level≥ 200 000 IU/mL (OR: 6.83; 95% CI: 1.61–29.00).Conclusion In low-income countries, the antenatal consultation provides a cost-effective opportunity to identify HBV-infected householdcontacts and link them to care. Children born before the introduction of infant hepatitis B vaccination and whose mother has higher viralload or infectivity should be a priority for testing and linkage to car

A Universidade colaborando na construção de um projeto de promoção da saúde: relato de experiência de um grupo de alunos de Medicina da Unicamp, Campinas, SP, Brasil

Este trabalho foi realizado com o objetivo de oferecer aos estudantes de graduação em Medicina da Universidade Estadual de Campinas (Unicamp) a vivência de ações de saúde pública, segundo princípios do Sistema Único de Saúde (SUS), por meio da elaboração de um projeto coletivo de promoção da saúde ocular de crianças de 0 a 7 anos. Para isto, foi aplicado um questionário para levantar as necessidades em relação à saúde ocular em uma amostra da população usuária do Centro de Saúde Jardim Santa Mônica em Campinas (SP), em 2003. Nele, percebeu-se a falta de informações sobre cuidados básicos com os olhos e de recursos e qualificação profissional para diagnóstico e tratamento, bem como o desconhecimento dos direitos à saúde e a ausência de medidas preventivas, principalmente para crianças. Foi desenvolvido, então, um projeto de ação e aprendizado com alunos, professores, agentes comunitários de saúde e auxiliares de uma creche do bairro, formando uma equipe de trabalho. Foram realizadas oficinas com essa equipe, na perspectiva da promoção e proteção da saúde ocular. Para a sustentabilidade do projeto, o planejamento previu a criação de um banco de óculos para a doação de armações e garantia da confecção para as pessoas com dificuldades financeiras. A experiência da construção e da aplicação do projeto permitiu o conhecimento, na prática, da organização dos serviços e a dinâmica do sistema de saúde, inclusive para compreender alguns limites e sugerir políticas públicas de saúde ocular que correspondam às necessidades da população, apontando-se o papel do médico no desencadeamento de um trabalho coletivo de compartilhamento de saberes e responsabilidades

The university collaborating in the construction of a health promotion project: report on an experience of a group of Medical Students at Unicamp, Campinas, SP, Brazil

The goal of this project was to promote eye health and provide eye care to children from 0 to 7 years of age and to offer to medical students of Unicamp the possibility of participating in practice in a public health action carried out according to the principles of the Brazilian Unified Health System (SUS - Sistema Único de Saúde). In 2003, a questionnaire was applied to a sample of users of the Jardim Santa Mônica Health Care Center in Campinas, SP. Analysis of the data there obtained revealed some deficiencies in the promotion of eye health such as lack of information about basic eye care, lack of resources for treatment, lack of information about the right to care by the Unified Health System and the absence of any preventive measures, mainly for children. Thus, a project was developed offering workshops for students, teachers, community health agents and personnel from a neighborhood nurser y-school to enable them to act as multipliers of the obtained knowledge and to initiate a process of awareness building. A spectacle bank was created in order to grant the sustainability of the project, offering the confection of eye glasses with frames donated by the population and lenses offered by the city government and some optic stores to needed persons. Through this experience the medical students could obtain some practical knowledge about the organization of health services and the dynamics of the health system, enabling them to understand some limitations and to suggest public eye health policies meeting the needs of the population. A closer study of this project shows not only how important this kind of action is for the most needed segments of society but also the role a doctor can play as someone able to convince people to go for their rights.Este trabalho foi realizado com o objetivo de oferecer aos estudantes de graduação em Medicina da Universidade Estadual de Campinas (Unicamp) a vivência de ações de saúde pública, segundo princípios do Sistema Único de Saúde (SUS), por meio da elaboração de um projeto coletivo de promoção da saúde ocular de crianças de 0 a 7 anos. Para isto, foi aplicado um questionário para levantar as necessidades em relação à saúde ocular em uma amostra da população usuária do Centro de Saúde Jardim Santa Mônica em Campinas (SP), em 2003. Nele, percebeu-se a falta de informações sobre cuidados básicos com os olhos e de recursos e qualificação profissional para diagnóstico e tratamento, bem como o desconhecimento dos direitos à saúde e a ausência de medidas preventivas, principalmente para crianças. Foi desenvolvido, então, um projeto de ação e aprendizado com alunos, professores, agentes comunitários de saúde e auxiliares de uma creche do bairro, formando uma equipe de trabalho. Foram realizadas oficinas com essa equipe, na perspectiva da promoção e proteção da saúde ocular. Para a sustentabilidade do projeto, o planejamento previu a criação de um banco de óculos para a doação de armações e garantia da confecção para as pessoas com dificuldades financeiras. A experiência da construção e da aplicação do projeto permitiu o conhecimento, na prática, da organização dos serviços e a dinâmica do sistema de saúde, inclusive para compreender alguns limites e sugerir políticas públicas de saúde ocular que correspondam às necessidades da população, apontando-se o papel do médico no desencadeamento de um trabalho coletivo de compartilhamento de saberes e responsabilidades.20020

Fate of melatonin orally administered in preterm newborns: Antioxidant performance and basis for neuroprotection

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age <= 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns