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Introduction: Although healthcare workers (HCWs) have reported mental health problems since the beginning of the COVID-19 pandemic, they rarely use psychological support. Here, we described the use of psychological support among HCWs in Spain over the 2-year period following the initial pandemic outbreak and explore its association with workplace- and COVID-19-related factors measured at baseline, in 2020. Materials and methods: We conducted a longitudinal study on HCWs working in Spain. We used an online survey to collect information on sociodemographic characteristics, depressive symptoms, workplace- and COVID-19-related variables, and the use of psychological support at three time points (2020, 2021, and 2022). Data was available for 296, 294, and 251 respondents, respectively at time points 1, 2, and 3. Results: Participants had a median age of 43 years and were mostly females (n = 242, 82%). The percentage of HCWs using psychological support increased from 15% in 2020 to 23% in 2022. Roughly one in four HCWs who did not use psychological support reported symptoms compatible with major depressive disorder at follow up. Baseline predictors of psychological support were having to make decisions about patients' prioritisation (OR 5.59, 95% CI 2.47, 12.63) and probable depression (wave 2: OR 1.12, 95% CI 1.06, 1.19; wave 3: OR 1.10, 95% CI 1.04, 1.16). Conclusions: Our results suggest that there is call for implementing mental health promotion and prevention strategies at the workplace, along with actions to reduce barriers for accessing psychological support. [ABSTRACT FROM AUTHOR]

Objective: To examine any prospective association between neutrophil-to-lymphocyte ratio (NLR) at hospital admission and subsequent delirium in older COVID-19 hospitalized patients comparing by sex and age groups. Methods: The sample consisted of 1,785 COVID-19 adult inpatients (minimum sample size required of 635 participants) admitted to a public general hospital in Madrid (Spain) between March 16th and April 15th, 2020. Variables were obtained from electronic health records. Binary logistic regression models were performed between baseline NLR and delirium adjusting for age, sex, medical comorbidity, current illness severity, serious mental illness history and use of chloroquine and dexamethasone. An NLR cut-off was identified, and stratified analyses were performed by age and sex. Also, another biomarker was tested as an exposure (the systemic immune-inflammation index –SII). Results: 55.3% of the patients were men, with a mean age of 66.8 years. Roughly 13% of the patients had delirium during hospitalization. NLR on admission predicted subsequent delirium development (adjusted OR = 1.02, 95 percent CI: 1.00–1.04, p = 0.024). Patients between 69 and 80 years with NLR values > 6.3 presented a twofold increased risk for delirium (p = 0.004). There were no sex differences in the association between baseline NLR and delirium (p > 0.05) nor SII predicted delirium development (p = 0.341). Conclusion: NLR is a good predictor of delirium during hospitalization, especially among older adults, independently of medical comorbidity, illness severity, and other covariates. Routine blood tests on admission might provide valuable information to guide the decision-making process to be followed with these especially vulnerable patients. [ABSTRACT FROM AUTHOR]

To compare the effect of a mindfulness-based mobile application versus an in-person mindfulness-based training program in terms of reducing anxiety and increasing empathy, self-compassion, and mindfulness in a population of healthcare students. The authors conducted a single-blind, randomised controlled trial with three parallel groups. Participants were allocated to the mobile app, the in-person mindfulness-based program (IMBP), or a control group. Assessments at baseline and postintervention (8 weeks) included measures of anxiety, empathy, self-compassion, and mindfulness. Of 168 students randomised, 84 were analysed on an intention-to-treat basis (app: n = 31; IMBP: n = 23; control: n = 30). The mobile app group showed a large effect size for reductions in trait anxiety compared with controls (g = 0.85, p = 0.003), and a medium, nonsignificant effect compared with the IMBP group (g = 0.52, p = 0.152). Participants from both interventions experienced a significant increase in self-compassion and mindfulness compared with controls. Levels of empathy remained unchanged for the 3 arms. A mobile app can be as effective as an IMBP in reducing anxiety and increasing self-compassion and mindfulness among healthcare students. [ABSTRACT FROM AUTHOR]

Background: Legionella testing conducted at environmental laboratories plays an essential role in assessing the risk of disease transmission associated with water systems. However, drawbacks of culture-based methodology used for Legionella enumeration can have great impact on the results and interpretation which together can lead to underestimation of the actual risk. Up to 20% of the samples analysed by these laboratories produced inconclusive results, making effective risk management impossible. Overgrowth of competing microbiota was reported as an important factor for culture failure. For quantitative polymerase chain reaction (qPCR), the interpretation of the results from the environmental samples still remains a challenge. Inhibitors may cause up to 10% of inconclusive results. This study compared a quantitative method based on immunomagnetic separation (IMS method) with culture and qPCR, as a new approach to routine monitoring of Legionella. Results: First, pilot studies evaluated the recovery and detectability of Legionella spp using an IMS method, in the presence of microbiota and biocides. The IMS method results were not affected by microbiota while culture counts were significantly reduced (1.4 log) or negative in the same samples. Damage by biocides of viable Legionella was detected by the IMS method. Secondly, a total of 65 water samples were assayed by all three techniques (culture, qPCR and the IMS method). Of these, 27 (41.5%) were recorded as positive by at least one test. Legionella spp was detected by culture in 7 (25.9%) of the 27 samples. Eighteen (66.7%) of the 27 samples were positive by the IMS method, thirteen of them reporting counts below 103 colony forming units per liter (CFU l−1), six presented interfering microbiota and three presented PCR inhibition. Of the 65 water samples, 24 presented interfering microbiota by culture and 8 presented partial or complete inhibition of the PCR reaction. So the rate of inconclusive results of culture and PCR was 36.9 and 12.3%, respectively, without any inconclusive results reported for the IMS method. Conclusion: The IMS method generally improved the recovery and detectability of Legionella in environmental matrices, suggesting the possibility to use IMS method as valuable indicator of risk. Thus, this method may significantly improve our knowledge about the exposure risk to these bacteria, allowing us to implement evidence-based monitoring and disinfection strategies. [ABSTRACT FROM AUTHOR]

Gamma tocopherol (gT) exhibits beneficial cardiovascular effects partly due to its anti-inflammatory activity. Important sources of gT are vegetable oils. However, little is known to what extent gT can be transferred into marine animal species such as Atlantic salmon by feeding. Therefore, in this study we have investigated the transfer of dietary gT into salmon. To this end, fish were fed a diet supplemented with 170 ppm gT for 16 weeks whereby alpha tocopherol levels were adjusted to 190 ppm in this and the control diet. Feeding gT-rich diets resulted in a three-fold increase in gT concentrations in the liver and fillet compared to non-gT-supplemented controls. Tissue alpha tocopherol levels were not decreased indicating no antagonistic interaction between gamma- and alpha tocopherol in salmon. The concentration of total omega 3 fatty acids slightly increased in response to dietary gT. Furthermore, dietary gT significantly decreased malondialdehyde in the fillet, determined as a biomarker of lipid peroxidation. In the liver of gT fed salmon we observed an overall down-regulation of genes involved in lipid homeostasis. Additionally, gT improved the antioxidant capacity by up-regulating Gpx4a gene expression in the pyloric caeca. We suggest that Atlantic salmon may provide a marine functional source capable of enriching gT for human consumption. [ABSTRACT FROM AUTHOR]

Background The presence of depressive subsyndromal symptoms (SS) in bipolar disorder (BD) increases the risk of affective relapse and worsens social, cognitive functioning, and quality of life. Nonetheless, there are limited data on how to optimize the treatment of subthreshold depressive symptoms in BD. Mindfulness-Based Cognitive Therapy (MBCT) is a psychotherapeutic intervention that has been shown effective in unipolar depression. The assessment of its clinical effectiveness and its impact on biomarkers in bipolar disorder patients with subsyndromal depressive symptoms and psychopharmacological treatment is needed. Methods/design A randomized, multicenter, prospective, versus active comparator, evaluator-blinded clinical trial is proposed. Patients with BD and subclinical or mild depressive symptoms will be randomly allocated to: 1) MBCT added to psychopharmacological treatment; 2) a brief structured group psychoeducational intervention added to psychopharmacological treatment; 3) standard clinical management, including psychopharmacological treatment. Assessments will be conducted at screening, baseline, post-intervention (8 weeks) and 4 month follow-up post-intervention. The aim is to compare MBCT intervention versus a brief structured group psychoeducation. Our hypothesis is that MBCT will be more effective in reducing the subsyndromal depressive symptoms and will improve cognitive performance to a higher degree than the psychoeducational treatment. It is also hypothesized that a significant increase of BDNF levels will be found after the MBCT intervention. Discussion This is the first randomized controlled trial to evaluate the effects of MBCT compared to an active control group on depressive subthreshold depressive symptoms in patients with bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. Methods: In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. Results: Of the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15). Conclusions: Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART. [ABSTRACT FROM AUTHOR]

Background This study aims to explore differences in personal narratives of the experience of illness and treatment in depressed oncologic patients who received either combined treatment for depression (psychotherapy plus antidepressants) or standard treatment (antidepressants alone). Methods We employed a qualitative research design based on grounded theory. Data were collected from eight videotaped focus groups and semi-structured interviews with a total of 28 participants. The research team reviewed interview transcripts and categorized the participants' responses using the ATLAS.ti (ATLAS.ti Scientific Software Development GmbH Hardenbergstr. 7 D-10623, Berlin) software package. Results Compared with patients in the standard treatment group, patients in the combined treatment group were better able to relate their experiences of physical and emotional discomfort and find meaning in the experience of illness by viewing cancer as a transformative experience. In addition, patients in the combined treatment group tended to use more active coping strategies based on acceptance of their situation and emphasized that psychotherapy had been helpful. Conclusions Qualitative analysis is an efficient method of examining the meaning of quantitative results in depth, particularly patients' perspectives on quality of life. Patients undergoing combined treatment consider psychotherapy to be a helpful tool and exhibit more personal growth than do patients undergoing standard treatment. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study was conducted to assess the prevalence of depressive symptoms, sleep disturbances, and subjective cognitive complaints in patients with HIV receiving highly active antiretroviral therapy. Participants completed the “Center for Epidemiological Studies Depression Scale” (CES-D) and a questionnaire on sleep disturbances and subjective cognitive complaints. Mean age of the 799 participants was 43.7 years and 67% were men. Adjusted prevalence of CES-D was 35.4% (95% confidence interval [CI]: 32.0-38.7), with no significant differences between gender and age groups. Sleep disturbances were more prevalent in older versus younger participants (74.0% [95% CI: 70.4-77.7] versus 63.3% [95% CI: 56.8-69.8]). Cognitive complaints were more prevalent in women (52.3% [95% CI: 46.4-58.2]) when compared with men (48.2% [95% CI: 44.7-51.6]). Hepatitis C virus coinfection was a strong predictor of depressive symptoms. Male gender and detectable viral load were independent risk factors for sleep disturbance. A higher CES-D score was an independent risk factor for sleep disturbance and cognitive complaints. [ABSTRACT FROM PUBLISHER]

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A letter to the editor is presented in response to the article on the diagnosis of the first case of secondary-ebola virus disease (EVD) outside Africa in Spain in the October 6, 2014 issue.

Background: Evidence-based mental health interventions to support healthcare workers (HCWs) in crisis settings are scarce., Objective: To evaluate the capacity of a mental health intervention in reducing anxiety and depression symptoms in HCWs, relative to enhanced care as usual (eCAU), amidst the COVID-19 pandemic., Methods: We conducted an analyst-blind, parallel, multicentre, randomised controlled trial. We recruited HCWs with psychological distress from Madrid and Catalonia (Spain). The intervention arm received a stepped-care programme consisting of two WHO-developed interventions adapted for HCWs: Doing What Matters in Times of Stress (DWM) and Problem Management Plus (PM+). Each intervention lasted 5 weeks and was delivered remotely by non-specialist mental health providers. HCWs reporting psychological distress after DWM completion were invited to continue to PM+. The primary endpoint was self-reported anxiety/depression symptoms (Patient Health Questionnaire-Anxiety and Depression Scale) at week 21., Findings: Between 3 November 2021 and 31 March 2022, 115 participants were randomised to stepped care and 117 to eCAU (86% women, mean age 37.5). The intervention showed a greater decrease in anxiety/depression symptoms compared with eCAU at the primary endpoint (baseline-adjusted difference 4.4, 95% CI 2.1 to 6.7; standardised effect size 0.8, 95% CI 0.4 to 1.2). No serious adverse events occurred., Conclusions: Brief stepped-care psychological interventions reduce anxiety and depression during a period of stress among HCWs., Clinical Implications: Our results can inform policies and actions to protect the mental health of HCWs during major health crises and are potentially rapidly replicable in other settings where workers are affected by global emergencies., Trial Registration Number: NCT04980326., Competing Interests: Competing interests: A-LP, AM-M, CB, DM, JLA-M and MS received support from the European Commission for the submitted work (grant number: 101016127). MS is president of the International Society for Traumatic Stress Studies. RK has received personal advisory honoraria from Joy Ventures (Herzlia, Israel) and is secretary of the International Resilience Alliance (Mainz, Germany)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. Published by BMJ.)

Background: Healthcare workers (HCWs) from COVID-19 hotspots worldwide have reported poor mental health outcomes since the pandemic's beginning. The virulence of the initial COVID-19 surge in Spain and the urgency for rapid evidence constrained early studies in their capacity to inform mental health programs accurately. Here, we used a qualitative research design to describe relevant mental health problems among frontline HCWs and explore their association with determinants and consequences and their implications for the design and implementation of mental health programs., Materials and Methods: Following the Programme Design, Implementation, Monitoring, and Evaluation (DIME) protocol, we used a two-step qualitative research design to interview frontline HCWs, mental health experts, administrators, and service planners in Spain. We used Free List (FL) interviews to identify problems experienced by frontline HCWs and Key informant (KI) interviews to describe them and explore their determinants and consequences, as well as the strategies considered useful to overcome these problems. We used a thematic analysis approach to analyze the interview outputs and framed our results into a five-level social-ecological model (intrapersonal, interpersonal, organizational, community, and public health)., Results: We recruited 75 FL and 22 KI interviewees, roughly balanced in age and gender. We detected 56 themes during the FL interviews and explored the following themes in the KI interviews: fear of infection, psychological distress, stress, moral distress, and interpersonal conflicts among coworkers. We found that interviewees reported perceived causes and consequences across problems at all levels (intrapersonal to public health). Although several mental health strategies were implemented (especially at an intrapersonal and interpersonal level), most mental health needs remained unmet, especially at the organizational, community, and public policy levels., Conclusions: In keeping with available quantitative evidence, our findings show that mental health problems are still relevant for frontline HCWs 1 year after the COVID-19 pandemic and that many reported causes of these problems are modifiable. Based on this, we offer specific recommendations to design and implement mental health strategies and recommend using transdiagnostic, low-intensity, scalable psychological interventions contextually adapted and tailored for HCWs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mediavilla, Monistrol-Mula, McGreevy, Felez-Nobrega, Delaire, Nicaise, Palomo-Conti, Bayón, Bravo-Ortiz, Rodríguez-Vega, Witteveen, Sijbrandij, Turrini, Purgato, Vuillermoz, Melchior, Petri-Romão, Stoffers-Winterling, Bryant, McDaid, Park, Ayuso-Mateos and RESPOND Consortium.)

Introduction: The COVID-19 outbreak is having an impact on the well-being of healthcare workers. Mindfulness-based interventions have shown effectiveness in reducing stress and fostering resilience and recovery in healthcare workers. There are no studies examining the feasibility of brief mindfulness-based interventions during the COVID-19 outbreak. Materials and Methods: This is an exploratory study with a post intervention assessment. We describe an on-site brief mindfulness intervention and evaluate its helpfulness, safety, and feasibility. Results: One thousand out of 7,000 (14%) healthcare workers from La Paz University Hospital in Madrid (Spain) participated in at least one session. One hundred and fifty out of 1,000 (15%) participants filled out a self-report questionnaire evaluating the helpfulness of the intervention for on-site stress reduction. Ninety two subjects (61%) participated in more than one session. Most of the participants were women (80%) with a mean age of 38.6 years. Almost half of the sample were nurses (46%). Sessions were perceived as being helpful with a mean rating of 8.4 on a scale from 0 to 10. Only 3 people (2%) reported a minor adverse effect (increased anxiety or dizziness). Discussion: Our data supports the utility, safety and feasibility of an on-site, brief mindfulness-based intervention designed to reduce stress for frontline health workers during a crisis. There is a need to continue testing this type of interventions, and to integrate emotion regulation strategies as an essential part of health workers' general training. Clinical Trial Registration number: NCT04555005., (Copyright © 2020 Rodriguez-Vega, Palao, Muñoz-Sanjose, Torrijos, Aguirre, Fernández, Amador, Rocamora, Blanco, Marti-Esquitino, Ortiz-Villalobos, Alonso-Sañudo, Cebolla, Curto, Villanueva, de-la-Iglesia, Carracedo, Casado, Vidal, Trigo, Iglesias, Cabañas, Mellado, García, Fernández-Encinas, Navarro, Mediavilla, Vidal-Villegas, Bravo-Ortiz and Bayón.)

The measures to contain the spread of the COVID-19 outbreak have no precedent in the recent history of many countries. Around 2,000 million people in the world are in isolation or quarantine, and gatherings of people have been expressly banned in many countries. In Spain, this prohibition affects workplaces, schools, and the national health system, where most of the healthcare is being provided either on the phone or online.

Objectives. The psychometric properties regarding sex and age for the revised version of the Temperament and Character Inventory (TCI-R) and its derived short version, the Temperament and Character Inventory (TCI-140), were evaluated with a randomized sample from the community. Methods. A randomized sample of 367 normal adult subjects from a Spanish municipality, who were representative of the general population based on sex and age, participated in the current study. Descriptive statistics and internal consistency according to α coefficient were obtained for all of the dimensions and facets. T-tests and univariate analyses of variance, followed by Bonferroni tests, were conducted to compare the distributions of the TCI-R dimension scores by age and sex. Results. On both the TCI-R and TCI-140, women had higher scores for Harm Avoidance, Reward Dependence and Cooperativeness than men, whereas men had higher scores for Persistence. Age correlated negatively with Novelty Seeking, Reward Dependence and Cooperativeness and positively with Harm Avoidance and Self-transcendence. Young subjects between 18 and 35 years had higher scores than older subjects in NS and RD. Subjects between 51 and 77 years scored higher in both HA and ST. The alphas for the dimensions were between 0.74 and 0.87 for the TCI-R and between 0.63 and 0.83 for the TCI-140. Conclusion. Results, which were obtained with a randomized sample, suggest that there are specific distributions of personality traits by sex and age. Overall, both the TCI-R and the abbreviated TCI-140 were reliable in the 'good-to-excellent' range. A strength of the current study is the representativeness of the sample.

In a cross-sectional study of aviremic neurocognitively impaired patients receiving protease inhibitors as triple-drug therapy (n = 30) or as monotherapy (n = 22), we found no statistically significant differences in the types of cognitive domains involved or severity of cognitive deficit. Cerebrospinal fluid concentrations of total proteins, total tau, myelin basic protein, neuron-specific enolase, β2 microglobulin, S100B protein, or prevalence of cerebrospinal fluid HIV-RNA detection by standard (6.3% vs 7.1% P = 1) or ultrasensitive assays (50% vs 71.4%, P = 0.28) were similar in both groups. These results do not suggest important differences in the pattern of neurocognitive impairment between groups receiving very different antiretroviral strategies.

Studies of patients with schizophrenia or schizophrenia spectrum disorders and general population control groups consistently show differences regarding personality dimensions. However, the profile of personality dimensions in first-degree relatives of those patients is not well understood. We used Temperament and Character Inventory to explore personality dimensions in 61 clinically stable patients with schizophrenia or schizophrenia spectrum disorders, 59 of their first-degree relatives, and 64 healthy controls. Patients scored significantly higher than controls in harm avoidance and self-transcendence and lower in self-directedness and cooperativeness. First-degree relatives showed a tendency to lower novelty seeking and self-transcendence than controls. Interpretations of these findings include the possibility that lower novelty seeking and lower self-transcendence provide a protective influence in the relatives. Further studies are needed to go into this issue in greater depth.

Objective: Congenital defects remain the second cause of perinatal and infant death and the third cause between the second and fifth years of life in Asturias. These anomalies generate substantial morbidity. The aim of the present study was to describe the population-based frequency of congenital defects in Asturias and their forms of presentation., Methods: Data from the population-based Registry of Congenital Defects of Asturias for 1990-2004 were analyzed. The data related to live births, stillbirths and induced abortions after prenatal diagnosis and are presented as birth prevalence and total prevalence (including induced abortions)., Results: The total number of births was 103,452 and there were 3,035 cases of congenital defects, representing a total prevalence of 2.9 cases per 100 births and a birth prevalence of 2.5%. These figures showed a tendency to increase throughout the study period. A total of 2,516 (82.9%) cases were live births, 46 (1.5%) were stillbirths and 473 (15.6%) were induced abortions. Prenatal diagnosis increased throughout the period. Sixtythree percent of total cases showed an isolated defect, 17% a recognized syndrome and the remaining 20% had multiple malformations without a syndromic pattern. The most frequent and severe defects registered were neural tube defects (12.2 per 10,000 births), chromosomal abnormalities (34.4 per 10,000), and cardiac defects (75.2 per 10,000)., Conclusions: The 15-year experience of the Registry of Congenital Defects of Asturias reveals the utility of this type of database to evaluate prenatal screening programs, plan the resources needed in affected pregnant women and infants, and perform epidemiological surveillance of congenital defects in relation to environmental risks, drug exposure and assisted reproduction techniques.

Background: Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-alpha have been demonstrated in thyroid follicular cells and TNF-alpha and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-alpha have been reported to be elevated and administration of TNF-alpha to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome., Objective: To evaluate serum concentrations of TNF-alpha and the soluble receptor for TNF-alpha (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy., Design: We studied 20 patients with hypothyroidism (18 women and 2 men, mean age +/- SD, 48.8 +/- 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 +/- 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 +/- 15.1 years) were also studied as a control group., Setting: All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic., Measurements: Serum concentrations of free T4 (FT4), total T3, TSH, TNF-alpha and sTNFR-I were measured in all subjects. TNF-alpha and sTNFR-I were measured using a quantitative enzyme immunoassay., Results: In patients with hypothyroidism serum concentrations of TNF-alpha (3.17 +/- 1.18 pg/ml) and sTNFR-I (1273 +/- 364 pg/ml) were significantly higher than those found in controls (2.42 +/- 0.76 pg/ml, P < 0.05, and 971 +/- 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with l-thyroxine therapy did not significantly modify TNF-alpha or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-alpha and sTNFR-I in patients with autoimmune (n = 14) or nonautoimmune (n = 6) hypothyroidism. Before therapy, patients with hyperthyroidism showed elevated serum concentrations of TNF-alpha (3.36 +/- 1.21 pg/ml; P < 0.01) and sTNFR-I (2274 +/- 579 pg/ml; P < 0.001) in relation to the control group. Treatment of hyperthyroidism was accompanied by a normalization of TNF-alpha levels (2.46 +/- 0.89 pg/ml; P < 0.001) and by a significant decrease in sTNFR-I concentrations (1369 +/- 475 pg/ml; P < 0.001). Post-therapy levels of TNF-alpha and sTNFR-I showed a significant correlation with loss of weight (r = 0.674, P < 0.01, and r = 0.629, P < 0.01, respectively) in hypothyroid patients. No correlation between these parameters was found in the group of patients with hyperthyroidism., Conclusions: In summary, these results confirm the relevance of activation of the TNF-alpha system in patients with thyroid dysfunction, as high plasma concentrations of TNF-alpha and sTNFR-I have been demonstrated in patients with hypothyroidism or hyperthyroidism. Treatment of hyperthyroidism is accompanied by a significant reduction in the previously elevated concentrations of both TNF-alpha and sTNFR-I. However, these changes are not seen when normalizing thyroid function in patients with hypothyroidism.