Systematic design of health monitoring systems centered on older adults and ADLs.

BACKGROUND: Older adults face unique health challenges as they age, including physical and mental health issues and mood disorders. Negative emotions and social isolation significantly impact mental and physical health. To support older adults and address these challenges, healthcare professionals can use Information and Communication Technologies (ICTs) such as health monitoring systems with multiple sensors. These systems include digital biomarkers and data analytics that can streamline the diagnosis process and help older adults to maintain their independence and quality of life. METHOD: A design research methodology is followed to define a conceptual model as the main artifact and basis for the systematic design of successful systems centered on older adults monitoring within the health domain. RESULTS: The results include a conceptual model focused on older adults' Activities of Daily Living (ADLs) and Health Status, considering various health dimensions, including social, emotional, physical, and cognitive dimensions. We also provide a detailed instantiation of the model in real use cases to validate the usefulness and feasibility of the proposal. In particular, the model has been used to develop two health systems intended to measure the degree of the elders' frailty and dependence with biomarkers and machine learning. CONCLUSIONS: The defined conceptual model can be the basis to develop health monitoring systems with multiple sensors and intelligence based on data analytics. This model offers a holistic approach to caring for and supporting older adults as they age, considering ADLs and various health dimensions. We have performed an experimental and qualitative validation of the proposal in the field of study. The conceptual model has been instantiated in two specific case uses, showing the provided abstraction level and the feasibility of the proposal to build reusable, extensible and adaptable health systems. The proposal can evolve by exploiting other scenarios and contexts.

Fish oil supplementation counteracts the effect of high-fat and high-sucrose diets on the carbonylated proteome in the rat cerebral cortex.

High daily intake of saturated fats and refined carbohydrates, which often leads to obesity and overweight, has been associated with cognitive impairment, premature brain aging and the aggravation of neurodegenerative diseases. Although the molecular pathology of obesity-related brain damage is not fully understood, the increased levels of oxidative stress induced by the diet seem to be definitively involved. Being protein carbonylation determinant for protein activity and function and a main consequence of oxidative stress, this study aims to investigate the effect of the long-term high-fat and sucrose diet intake on carbonylated proteome of the cerebral cortex of Sprague-Dawley rats. To achieve this goal, the study identified and quantified the carbonylated proteins and lipid peroxidation products in the cortex, and correlated them with biometrical, biochemical and other redox status parameters. Results demonstrated that the obesogenic diet selectively increased oxidative damage of specific proteins that participate in fundamental pathways for brain function, i.e. energy production, glucose metabolism and neurotransmission. This study also evaluated the antioxidant properties of fish oil to counteract diet-induced brain oxidative damage. Fish oil supplementation demonstrated a stronger capacity to modulate carbonylated proteome in the brain cortex. Data indicated that fish oils did not just decrease carbonylation of proteins affected by the obesogenic diet, but also decreased the oxidative damage of other proteins participating in the same metabolic functions, reinforcing the beneficial effect of the supplement on those pathways. The results could help contribute to the development of successful nutritional-based interventions to prevent cognitive decline and promote brain health.

Antiparasitic Tannin-Rich Plants from the South of Europe for Grazing Livestock: A Review.

Internal parasites are one of the main causes of health threats in livestock production, especially in extensive livestock farming. Despite the environmental toxic effects (loss of dung beetles, biodiversity, and other issues) and resistance phenomenon derived from their prolonged use, anti-parasitic chemical pharmaceuticals are frequently used, even in organic farming. Such a situation within the context of climate change requires urgent exploration of alternative compounds to solve these problems and apparent conflicts between organic farming objectives regarding the environment, public health, and animal health. This review is focused on some plants (Artemisia spp., Cichorium intybus L., Ericaceae family, Hedysarum coronarium L., Lotus spp., Onobrychis viciifolia Scop.) that are well known for their antiparasitic effect, are voluntarily grazed and ingested, and can be spontaneously found or cultivated in southern Europe and other regions with a Mediterranean climate. The differences found between effectiveness, parasite species affected, in vitro/in vivo experiments, and active compounds are explored. A total of 87 papers where antiparasitic activity of those plants have been studied are included in this review; 75% studied the effect on ruminant parasites, where gastrointestinal nematodes were the parasite group most studied (70%), and these included natural (31%) and experimental (37%) infections.

Effectiveness and safety of a microcrystalline tyrosine-adjuvanted Dermatophagoides pteronyssinus allergoid immunotherapy in adult patients with allergic asthma and rhinitis: A real-life prospective observational study.

INTRODUCTION: Although clinical trials have shown the efficacy and safety of allergen-specific immunotherapy (AIT) in the treatment of allergic asthma, there is a need for real-life studies. We aimed to assess the effectiveness and safety of a microcrystalline tyrosine-adjuvanted Dermatophagoides pteronyssinus allergoid (Acarovac Plus®) in patients with house dust mite (HDM)-induced allergic asthma in a real-life study. METHODS: A subanalysis of a multicenter, prospective, observational, real-life study. Patients with rhinitis and allergic asthma caused by HDMs were assessed before AIT with Acarovac Plus® and at 6 and 12 months after this treatment. Assessment parameters were percentage of days with asthma symptoms, percentage of days on asthma medication, classification of asthma according to Spanish guidelines for the management of asthma, asthma-related quality of life (quality of life in adults with asthma questionnaire [QLAAQ]), perception of symptoms (visual analog scale [VAS]), and treatment satisfaction (treatment satisfaction questionnaire for medication [TSQM]). Safety was assessed by the number and severity of adverse reactions. RESULTS: This subanalysis included 55 patients. Treatment with Acarovac Plus® showed significant differences in the analyzed variables when the baseline visit was compared with the 12-month visit: reduction of the mean (SD) percentage of days with asthma symptoms (23.9 [9.2] vs. 5.1 [12.8]; p = .002), of the mean [SD] percentage of days on asthma medication (67.6 [42.9] vs. 45.1 [46.8]; p = .002), and of the percentage of patients with persistent asthma (78.2% vs. 38.9%; p = .009). Acarovac Plus® significantly improved asthma-related quality of life, as shown by a decrease of 1.39 points in QLAAQ score at 12 months (p < .001), and in the subjective perception of symptoms on the VAS (-3.50, p < .0001). Patients showed high treatment satisfaction according to the TSQM, and it was well tolerated. No serious adverse events were reported. CONCLUSIONS: Acarovac Plus® was effective and safe for the treatment of patients with HDM-induced allergic asthma in a real-life study.

Safety and effectiveness of sucroferric oxyhydroxide in Spanish patients on dialysis: sub-analysis of the VERIFIE study.

BACKGROUND AND AIMS: In this study, we show the results of the subset of Spanish patients of the VERIFIE study, the first post-marketing study assessing the long-term safety and effectiveness of sucroferric oxyhydroxide (SFOH) in patients with hyperphosphatemia undergoing dialysis during clinical practice. PATIENTS AND METHODS: Patients undergoing hemodialysis and peritoneal dialysis with indication of SFOH treatment were included. Follow-up duration was 12-36 months after SFOH initiation. Primary safety variables were the incidence of adverse drug reactions (ADRs), medical events of special interest (MESIs), and variations in iron-related parameters. SFOH effectiveness was evaluated by the change in serum phosphorus levels. RESULTS: A total of 286 patients were recruited and data from 282 were analyzed. Among those 282 patients, 161 (57.1%) withdrew the study prematurely and 52.5% received concomitant treatment with other phosphate binders. ADRs were observed in 35.1% of patients, the most common of which were gastrointestinal disorders (77.1%) and mild/moderate in severity (83.7%). MESIs were reported in 14.2% of patients, and 93.7% were mild/moderate. An increase in ferritin (386.66ng/mL vs 447.55ng/mL; p=0.0013) and transferrin saturation (28.07% vs 30.34%; p=0.043) was observed from baseline to the last visit (p=0.0013). Serum phosphorus levels progressively decreased from 5.69mg/dL at baseline to 4.84mg/dL at the last visit (p<0.0001), increasing by 32.2% the proportion of patients who achieved serum phosphorus levels ≤5.5mg/dL, with a mean daily SFOH dose of 1.98 pills/day. CONCLUSIONS: SFOH showed a favorable effectiveness profile, a similar safety profile to that observed in the international study with most adverse events of mild/moderate severity, and a low daily pill burden in Spanish patients in dialysis.

Immunological parameters as biomarkers of response to MicroCrystalline Tyrosine-adjuvanted mite immunotherapy.

BACKGROUND: Despite the effectiveness of allergen immunotherapy (AIT), some patients are unresponsive for reasons still unknown; yet validated response biomarkers remain unavailable. OBJECTIVE: To analyze immunological parameters as biomarkers to monitor and predict clinical response to a MicroCrystalline Tyrosine-adjuvanted house dust mite (HDM) AIT in patients with allergic rhinitis (AR). METHODS: Observational, prospective, multicenter study including adult patients (aged 18-65 years) with AR, with and without asthma, sensitized to the HDM Dermatophagoides pteronyssinus (DP) and prescribed Acarovac Plus® DP 100% in the routine practice. Serum concentrations of total IgE, specific IgE, specific IgG4, IL-4, IL-5, IL-10, IL-13, and IFN-γ were compared between baseline and 12 months after AIT. The relationship between patients' baseline immunological profiles and classification as low, high, and non-responders and between their sensitization profile to DP allergens and effectiveness were analyzed. RESULTS: Of 141 patients recruited, 118 (mean [SD] age of 33.6 [9.5] years) were evaluable. One year after treatment, Der p 1-specific IgE, DP-specific IgG4, and IL-10 increased by a mean (SD) of 3.4 (13.6) kU/L (p = 0.016), 0.43 (0.55) mg/L (p < 0.0001), and 1.35 (7.56) pg/mL (p = 0.033), respectively. Non-responders showed increased baseline levels of IL-13 compared to high responders (p = 0.037). Changes in effectiveness variables between baseline and after AIT were similar regardless of the sensitization profile. CONCLUSION: Non-responsive patients to AIT showed increased baseline IL-13 concentrations, suggesting its value as prognostic biomarker. DP-specific AIT increased Der p 1-specific IgE, DP-specific IgG4, and IL-10 concentrations in patients with AR. All patients benefited from treatment regardless of their sensitization profile to major DP allergens.

Cytotoxicity studies of a stilbene extract and its main components intended to be used as preservative in the wine industry.

The use of stilbenes has been proposed as an alternative to sulfur dioxide in wine. Provided the feasibility from a technological approach, the cytotoxicity of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99 extract) was assessed in the human cell lines HepG2 and Caco-2. In addition, the effects of the main stilbenes found in ST-99, trans-resveratrol and trans-ε-viniferin were studied, as well as its mixture. Similar cytotoxic effects were obtained in the exposures to trans-ε-viniferin, ST-99 and the mixture; however, trans-resveratrol alone exerted less toxicity. When HepG2 cells were exposed to trans-ε-viniferin, ST-99 and the mixture, the mean effective concentration (EC50) were 28.28 ± 2.15, 31.91 ± 1.55 and 29.47 ± 3.54 µg/mL, respectively. However, in the exposure to trans-resveratrol, the EC50 was higher 50 µg/mL. The morphological study evidenced damage at ultrastructural level in HepG2 cells, highlighting the inhibition of cell proliferation and the induction of apoptosis. The type of interaction produced by trans-ε-viniferin and trans-resveratrol mixtures was assessed by an isobologram analysis using the CalcuSyn software, evidencing an antagonist effect. These data comprise a starting point in the toxicological assessment; further studies are needed in this field to assure the safety of the extract ST-99.

Real-life effect of a microcrystalline tyrosine adjuvanted mite immunotherapy in patients with allergic rhinitis.

Aim: Evaluate the effectiveness and safety of immunotherapy with Acarovac Plus® in a 1-year prospective multicentered real-life study. Methods: A total of 118 adults with allergic rhinitis sensitized to Dermatophagoides received subcutaneous immunotherapy with Acarovac Plus. Treatment outcomes were evaluated at baseline, 6 months and 1 year after treatment initiation. Primary end point was the evolution of the combined symptom and medication score. Secondary end points included other effectiveness outcomes and measurement of product tolerability. Results: Acarovac Plus induced significant improvements in primary and secondary end points after 6 months compared with baseline. These differences persisted after 1 year of treatment (p < 0.001; baseline vs 1 year): combined symptom and medication score (1.60 vs 0.79). No serious adverse events were recorded. Conclusion: Acarovac Plus for 1 year was effective and well tolerated in a real-life setting.

Effect of phenolic extracts from different extra-virgin olive oil varieties on osteoblast-like cells.

The reported incidence of osteoporosis is lower in countries in which the Mediterranean diet predominates, and this apparent relationship may be mediated by the phenolic compounds present in olive oil. The objective of this study was to determine the effect of phenolic extracts from different varieties of extra-virgin olive oil (Picual, Arbequina, Picudo, and Hojiblanca) on the differentiation, antigenic expression, and phagocytic capacity of osteoblast-like MG-63 cells. At 24 h of treatment a significant increase in phosphatase alkaline activity and significant reductions in CD54, CD80, and HLA-DR expression and in phagocytic activity were observed in comparison to untreated controls. The in vitro study performed has demonstrated that phenolic compounds from different extra virgin olive oil varieties can modulate different parameters related to osteoblast differentiation and function.

Técnica semidirecta del atlas en rotación para una lesión de posterioridad / No disponible

La manipulación en rotación del atlas es la técnica manipulativa principal para poder corregir una posterioridad del atlas detectada con el test de flexión rotación del atlas, a la vez que suprime el espasmo de los músculos que pueden fijar la lesión. Está indicada en una lesión de rotación del atlas. Se realiza mediante un thrust directo sobre la posterioridad hacia el lado contrario, se considera una técnica de alta velocidad y corta amplitud

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The effect of low-level diode laser therapy on early differentiation of osteoblast via BMP-2/TGF-ß1 and its receptors.

OBJECTIVES: The objective of this study was to determine the effect of LLDL therapy on the gene expression of osteoblast markers of growth and differentiation. MATERIALS AND METHODS: The MG-63 cell line was exposed to diode laser (ezLase) of 940 nm at 1-1.5 W and 3-4 J, and gene expressions (Runx-2, alkaline phosphatase [ALP], type I collagen [Col-I], osterix [OSX], osteocalcin [OSC], osteoprotegerin [OPG], bone morphogenetic protein [BMP]-2 and -7, transforming growth factor-ß1 [TGF-ß1], and TGF-ß receptors [TGF-ß R1, TGF-ß R2; TGF-ß R3]) were evaluated by quantitative RT-PCR. RESULTS: LLDL treatment stimulated the expression of osteoblast differentiation markers ALP, Col-I, Runx-2, and OSX in relation to the doses applied (P < 0.05), but no changes were detected in OSC, OPG, or BMP-7 at any study dose. This effect may be mediated by TGF-ß1 and BMP-2, given that the treatment increased their expression and that of TGF-ß receptors R1, R2, and R3 (P < 0.001). CONCLUSION: These results suggest that the biostimulatory effect of laser therapy on osteoblasts may be attributable to the release of autocrine factors in response to the irradiation. A clinical trial is warranted to test its therapeutic usefulness in bone tissue regeneration and to define a treatment protocol.

Influencia postural de la técnica en rotación del atlas en pacientes con cervicalgia mecánica crónica / No disponible

Introducción: La cervicalgia mecánica crónica (CMC) es una patología común en la sociedad actual. Se define como dolor con una duración de al menos 3 meses desde el inicio de los síntomas, altera las funciones sensoriomotoras, y por tanto, la capacidad de mantener una postura correcta, incluyendo una reducción del rango de movimiento. Objetivos: Valorar el efecto de la manipulación en rotación del atlas (MRA) sobre la estabilometría en pacientes que padezcan: (i) dolor cervical de más de 3 meses de evolución y (ii) presenten un test de flexión-rotación cervical (TFRC) positivo. Material y Métodos: Estudio experimental, controlado, aleatorizado, doble ciego. Han participado 24 pacientes con CMC, 12 formaron parte del Grupo Experimental (GE) y 12 del Grupo Control (GC). Se midió la estabilometría con una plataforma de presiones, y el TFRC, estas mediciones se repitieron post-intervención inmediata, tras 7 y 15 días. Resultados: Encontramos que el gasto energético del paciente, para mantener la postura (L/S) mejora al final del estudio y se observa una mejora significativa (-79.20±5.45;p<0.001) a los 15 días, período en el que su organismo podría haberse adaptado a la nueva situación. Hay un claro aumento de los grados de rotación inmediatamente después de la manipulación (8.33±0.95;p<0.001). Conclusiones: La manipulación en rotación del atlas mejora la movilidad en rotación de la cabeza, y con el paso de los días hay una disminución en el esfuerzo para mantener la postura bípeda, con lo que mejora el gasto energético postural de los pacientes (AU)

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Green chromatography determination of fatty acid methyl esters in biodiesel.

This work proposes a green, simple and rapid chromatographic methodology for separation and determination of a group of 13 fatty acids methyl esters (FAMEs) by using a capillary gas chromatography with a flame ionization detector. The method was successfully applied for the determination of FAMEs in biodiesel samples from commercial and waste cooking oils, synthesized by homogeneous catalysis. Detection and quantification limits were in the µg L(-1) level. Direct injection of sample solution was compared with solid-phase extraction and solid-phase microextraction procedures, giving similar results. The lower analysis time represent considerable improvement compared with other papers. The described methodology is especially suitable for process control applications. The samples analysed showed total contents of FAMEs higher than 96.5%, which verifies the European regulations.

The effects of low-level diode laser irradiation on differentiation, antigenic profile, and phagocytic capacity of osteoblast-like cells (MG-63).

Previous in vivo and in vitro studies have reported that low-level diode laser therapy induces a biostimulatory effect, such as cell proliferation. The aim of the present study was to evaluate whether the laser irradiation of osteoblast-like cells (MG-63) can modify alkaline phosphatase activity (ALP), antigenic profile, and phagocytic capacity. The MG-63 cell line was exposed to diode laser (ezLase) of 940 nm at 1-1.5 W/cm(2) and 3-4 J. ALP was evaluated by a spectrophotometric technique and antigenic expression analysis (CD 54, CD80, CD86, HLA-DR), and phagocytic activity was analyzed by flow cytometry. At 24 h, the treated groups showed an increased ALP, and the highest increase versus controls (P = 0.002) was at the dose of 1 W/cm(2) and 3 J; this modulation of the antigenic profile translated into a reduced expression of CD54, CD86, and HLA-DR and a slightly decreased phagocytic capacity with respect to the nonirradiated control group at the different intensities and fluencies assayed. These results demonstrate that laser therapy can exert a biostimulatory effect on osteoblastic cells at different levels, which may be clinically useful in the regeneration of bone tissue.

Measurement of IgE to pollen allergen components is helpful in selecting patients for immunotherapy.

BACKGROUND: Pollen allergy still represents an important cause of allergic morbidity worldwide. Accurate diagnostic methods are important to determine the disease-causing allergen. OBJECTIVE: To describe the sensitization patterns of patients with spring pollinosis and to make a real-life evaluation of the usefulness of a predetermined IgE molecular profile compared with other sensitization methods for choosing the composition of immunotherapy. METHODS: One hundred seventy-five patients with a diagnosis of spring pollinosis completed a skin prick test study with Olea europaea, Phleum pratense, palm profilin, and peach peel and an in vitro study of the application of a specific recombinant IgE protocol (nOle e1, rPhl p1-5b, rPhl p12, rPhl p7, and rPru p3). Immunotherapy using the 2 methods was compared. RESULTS: A high sensitization to nOle e1 and rPhl p1-5b was found. Profilin, polcalcin, and lipid transfer proteins seemed irrelevant for the differential diagnosis of olea and grass pollen sensitization in the most southern area of the Iberian Peninsula. Application of the component resolved the diagnosis, and the choice of immunotherapy was changed in more than 50% of patients. CONCLUSION: These results support the necessity of the habitual use of this kind of protocol in routine allergologic practice.

PM2.5 mass and species trends in Santiago, Chile, 1998 to 2010: the impact of fuel-related interventions and fuel sales.

UNLABELLED: Improving air quality in Santiago has been a high priority for the Chilean government. In this paper we examine trends of fine particulate matter (PM2.5) mass and species concentrations during the period 1998 to 2010 and explore the impact of fuel-related interventions and fuel sales on concentration changes. Smoothing spline functions were utilized to characterize and account for nonlinear relationships between pollutant concentrations and different parameters. Meteorology-adjusted PM2.5 concentrations were lower by 21.8 microg/m3 in 2010 compared to 1998. In this model, wind speed was the most important determinant of PM2.5 levels. A decrease in 24-hr average wind speed below 1.0 m/s was associated with a significant increase in daily PM2.5 levels, indicating a high sensitivity of PM2.5 concentrations to the accumulation of local emissions. The same regression model framework was applied to examine the trends of lead, bromine, and sulfur concentrations. Removal of lead and bromine from gasoline achieved dramatic decreases in their atmospheric concentrations. Nonetheless, both elements continue to persist, likely in the form of PbBrCl. The reduction of diesel sulfur content from 1,500 to 50 ppm corresponded to a 32% decrease in particulate sulfur levels. Lastly, a surge in PM2.5 was observed in 2005-2008. Further regression analyses suggested this was prompted by a rise in monthly petroleum-based fuel sales. IMPLICATIONS: In this paper, we elucidate meteorology-adjusted trends of PM2.5 mass and species concentrations in Santiago and assess the efficacy of fuel-related interventions, such as the removal of lead from gasoline and reduction of sulfur content in diesel. In addition, we explore the impact of fuel sales on PM2.5 trends. Given that fuel consumption is likely to increase further in this rapidly growing city, understanding its impact on PM2.5 trends can inform future air quality control efforts in Santiago.

Decreased cerebrospinal fluid concentrations of substance P in treatment-resistant depression and lack of alteration after acute adjunct vagus nerve stimulation therapy.

Recent preclinical and clinical research has demonstrated that the neuropeptide substance P (SP) plays a role in the central nervous system (CNS) response to stress, and perhaps in the etiology of major depression and/or anxiety disorders. The nature of this role, however, is poorly understood. A limited body of evidence suggests that in medication-free depressed patients, cerebrospinal fluid (CSF) concentrations of SP may be elevated relative to healthy controls. Two studies have shown that antidepressant treatment does not significantly change CSF concentrations of SP. Using standard lumbar puncture techniques, baseline CSF samples were obtained from 19 medication-free healthy controls and 19 medicated patients with treatment-resistant depression (TRD). Mean CSF SP concentration was significantly lower in TRD patients on psychotropic medications than in the group of healthy subjects. After 10-12 weeks of treatment with adjunct vagus nerve stimulation (VNS), CSF SP concentrations were not significantly changed. Low CSF SP may reflect a biological marker of the subtype of severe and chronic depression that is resistant to standard therapies.

Acupuncture for depression: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of acupuncture as an intervention for major depressive disorder (MDD). METHOD: Acupuncture was examined in 151 patients with MDD (DSM-IV) who were randomly assigned to 1 of 3 groups in a double-blind randomized controlled trial. The specific intervention involved Traditional Chinese Medicine (TCM)-style acupuncture with manual stimulation for depression; the control conditions consisted of (1) a nonspecific intervention using a comparable number of legitimate acupuncture points not specifically targeted to depressive symptoms and (2) a waitlist condition, which involved waiting without intervention for 8 weeks. After 8 weeks, all patients received the depression-specific acupuncture. Each 8-week intervention regimen consisted of 12 acupuncture sessions delivered in an acupuncturist's office in the community. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression. The study was conducted from February 1998 to April 2002. RESULTS: Twenty patients terminated treatment before the completion of the 8-week intervention (13%) but not differentially by study group. Random regression models of the intent-to-treat sample revealed that although patients receiving acupuncture improved more than those awaiting intervention, no evidence of differential efficacy of the depression-specific over nonspecific intervention was found. Response rates in acupuncture-treated patients were relatively low after 8 weeks (22% and 39% for specific and nonspecific intervention groups, respectively), with the response rate after the entire 16-week trial reaching 50%. CONCLUSION: Although TCM manual acupuncture is a well-tolerated intervention, results fail to support its efficacy as a monotherapy for MDD. It can't be ruled out that factors unique to the implementation of acupuncture in this research study may have limited the efficacy of interventions compared to those provided in naturalistic settings. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00010517.

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study.

BACKGROUND: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.