Methotrexate treatment strategies for rheumatoid arthritis: a scoping review on doses and administration routes.

BACKGROUND: To describe the evidence of methotrexate (MTX) initiation strategies in patients with rheumatoid arthritis (RA) and, in the case of non-responders, analyse the efficacy and safety of route and dose optimisation. METHODS: We conducted a comprehensive scoping review of randomised controlled trials according to PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O'Malley. PubMed, EMBASE, and Cochrane were searched without language restriction, and hand searches of relevant articles were examined. RESULTS: We identified 1,367 potentially eligible studies, of which 12 were selected based on the titles and abstracts and then on the full-length articles. In naïve-MTX patients, a linear dose-response relationship for starting dose was found between 5 mg/m2/week (7.5-10 mg/week) and 10 mg/m2/week (15-22 mg/week), without toxicity correlation. A higher initial dose of MTX (25 mg vs. 15 mg) was more effective, resulting in fewer dose increases due to ineffectiveness and more dose reductions due to higher remission rates. There was also a trend towards increased gastrointestinal toxicity. Comparing different routes of administration of MTX, subcutaneous MTX showed a statistically higher ACR20 response (85%) in comparison with oral MTX (77%) (p < 0.05). The clinical efficacy and safety of accelerated and conventional start MTX regimens were comparable between 7.5 and 15 mg with a 2,5 mg dose increase every two weeks. In RA patients who have failed the initial treatment with MTX, the stepwise increase in MTX doses is associated with a higher ACR20 response and sustained remission rate than other strategies. In MTX non-responders, optimisation to SC MTX was associated with improvements in ACR20 and ACR50 rates with similar toxicity between groups. In the early RA patients subgroup, SC MTX showed higher ACR20 response rates than oral MTX, and intensive oral methods have a much higher sustained remission rate, shorter mean time to remission, and better clinical disease activity measures than conventional treatments. CONCLUSIONS: Higher starting doses of MTX and initial subcutaneous MTX made better performance in improving the ACR20 response, although the clinical effectiveness and safety of other MTX start regimens are comparable. This scoping review provides evidence in support of optimising MTX treatment in terms of route and dose prior to concluding that MTX treatment in RA patients has failed.

Spanish adaptation of the perinatal grief intensity scale.

AIMS/BACKGROUND: Assessing the intensity of perinatal grief is very important for identifying the more complex cases in mothers and fathers. Despite this, there are few assessment tools available. The aim of this study was to analyse the psychometric properties (factorial structure, reliability, and validity) of the Spanish version of the Perinatal Grief Intensity Scale (PGIS). DESIGN/METHODS: An online survey was completed by 291 mothers and fathers who had suffered perinatal loss in the previous six years. RESULTS: The results showed adequate fit indexes for the three-factor model of the PGIS: reality, confront others, and congruence. Reliability values for the overall scale and subscales were adequate. Finally, with regard to validity, significant (p < .05) and positive relationships were found with levels of complicated grief, event centrality, guilt, anxiety, and depression. There were also differences depending on whether participants exhibited high or low levels of complicated grief, and on the number of weeks of pregnancy at the time of the loss. CONCLUSION: In conclusion, the Spanish adaptation of the PGIS has adequate reliability and validity scores and a factorial structure consistent with the original version.

Emergency crisis resource management: a simulation-based course developed by the Spanish Society of Emergency Medicine (SEMES) for health sciences students. / Emergency Crisis Resource Management de la Sociedad Española de Medicina de Urgencias y Emergencias: curso de gestión en crisis basado en simulación para estudiantes de ciencias de la salud.

OBJECTIVES: Educational programs based on high-fidelity simulation training aim to promote students' acquisition of nontechnical competencies such as understanding crisis resource management (CRM). This study evaluated the efficacy of a CRM course for students in their last year of university studies in health sciences. The course was developed by the Spanish Society of Emergency Medicine (SEMES). MATERIAL AND METHODS: Quasi-experimental study of a high-fidelity simulation course to teach emergency CRM (E-CRM) using preand postcourse measures of achievement in a single student cohort. A total of 209 students completed 2 selfadministered self-efficacy evaluations of their acquisition of nontechnical competencies and resilience. External observers also assessed the students' nontechnical competencies with objective measurement scales. RESULTS: Scores on resilience and self-efficacy assessments improved through the intervention (F = 25.90 and F = 68.02, respectively; P .001, for both pre-post comparisons). Statistically significant differences were found between students in different health sciences at baseline (t = 2.67; P = .008). Scores improved significantly on the Mayo High Performance Teamwork Scale (F = 6.18, P .001, eta2 = 0.20) and the Ottawa CRM Global Rating Scale (F = 5.58; P .005, eta2 = 0.19). CONCLUSION: The E-CRM course developed by a coordinated multiprofessional team based on high-fidelity simulations improved self-efficacy assessments of resilience and all nontechnical competencies.

OBJETIVO: Los programas educativos dirigidos a la adquisición de competencias no técnicas, tales como el Crisis Resource Management (CRM), basado en simulación de alta fidelidad, implican un aumento de las competencias del alumno en el manejo de situaciones de crisis. El objetivo del presente trabajo es evaluar la eficacia del programa Emergency CRM (E-CRM) de la Sociedad Española de Medicina de Urgencias y Emergencias, dirigido a estudiantes de último año de los grados de ciencias de la salud. METODO: Se llevó a cabo un estudio cuasiexperimental con medidas pre y posintervención, que consistió en un programa de E-CRM con simulación de alta fidelidad, en un único grupo. Participaron un total de 209 estudiantes que completaron dos instrumentos autoadministrados sobre la autoeficacia hacia las competencias no técnicas y la resiliencia. Además, a través de observadores externos se evaluó sus competencias no técnicas con instrumentos de evaluación objetivos. RESULTADOS: El alumnado mejoró las puntuaciones de resiliencia (F = 25,90; p < 0,001) y autoeficacia (F = 68,02; p 0,001) tras la intervención, con diferencias estadísticamente significativas para la resiliencia en la línea basal en función del grupo de estudios (t = 2,67; p = 0,008). Por otro lado, se encontraron mejoras de las puntuaciones obtenidas tanto para el instrumento Mayo High Performance Teamwork Scale (F = 6,18; p 0,001; eta2 = 0,20) como para el Ottawa Global Rating Scale Crisis Resource Management (F = 5,58; p 0,005; eta2 = 0,19). CONCLUSIONES: El programa de E-CRM, basado en simulación de alta fidelidad, con un equipo interprofesional coordinado, mejora la autoeficacia en todas las competencias no técnicas medidas y aumenta la resiliencia.

Influence of menstrual pain and symptoms on activities of daily living and work absenteeism: a cross-sectional study.

OBJECTIVE: To examine the prevalence of menstrual pain among women of reproductive age and its impact on their daily lives and professional responsibilities. METHODS: A cross-sectional and descriptive study was conducted in July and August 2022. Phone interviews were carried out using a random system to select women aged between 15 and 49 years old. The questionnaire included sociodemographic variables, contraception method used, characteristics of the menstrual pattern (pain and bleeding amount), its influence on their working life, and if they would need to resort to sick leaves due to the impairments arising from the menstrual symptoms. RESULTS: A total of 1800 women representative of the Spanish population took part in this study. 72.6% of them report menstrual pain, with 45.9% requiring medication. 35.9% identify their menstrual bleeding as intense or very intense. 38.8% assert that menstrual discomforts affect their everyday life. 34.3% would have required not attending their work activities or having requested sick leave due to the discomforts, although only 17.3% of the women finally requested so, mainly because 58.4% considered that it might imply consequences in their professional environment, especially those with Higher Education. The women who report more discomfort are the youngest ones and those who resort to condoms as a contraceptive method (p < 0.001). CONCLUSIONS: Menstrual pain is a prevalent problem among women of reproductive age and can affect their everyday life and professional environment, requiring work leaves on some occasions.

This study is a starting point to know the prevalence of menstrual discomforts among Spanish women of reproductive age and their effect on the professional environment, to enable an assessment of the possible impact of the menstrual leave legislation recently implemented in Spain.

Spanish adaptation of the Stillbirth Stigma Scale (SSS).

The death of a baby in the perinatal period is considered a disenfranchized grief that can be a source of significant symptoms of guilt, shame, and stigma. There is a lack of validated instruments for assessing the stigma associated with perinatal grief. The aim of this study was to examine the psychometric properties (factor structure, reliability, and validity) of the Spanish version of the Stillbirth Stigma Scale (SSS) in parents who have experienced a perinatal loss. A total of 291 participants (mostly mothers) completed an online questionnaire that included the SSS and other measures. The best-fitting factor structure was a second-order model with four dimensions and adequate reliability values. In terms of validity, we found statistically significant relationships between the SSS scores and the variables of self-esteem, complicated grief, event centrality, depression, and anxiety. In conclusion, the Spanish adaptation of the SSS is deemed to have adequate psychometric properties.

Effectiveness of nursing interventions in the prevention of falls in older adults in the community and in health care settings: A systematic review and meta-analysis of RCT.

OBJECTIVE: To estimate the effectiveness of fall prevention programs in people aged 65 years and older involving nursing professionals. METHODS: We included available full-text randomized clinical trials on nurse-led prevention of falls in the community in people over 65 years of age and reporting the incidence of such falls. An extensive search was performed in 14 databases covering the period 2016-2018 for publications in English, French, Portuguese and Spanish. The quality of the papers was assessed independently and blindly by reviewers working in pairs using the risk of bias dominios of the Cochrane Collaboration. The hazard ratio was used as a measure of the effect size of the incidence of falls. A random-effects model was assumed for statistical analyses. The influence of moderator variables of the studies on the effect sizes was performed using ANOVAs and its 95% CI for each moderator category. RESULTS: A total of 31 randomized clinical trials were selected with 25,551 participants. The most frequent type of intervention was education (57.1%), followed by multifactorial models (37.1%). The probability of falling was significantly reduced by 13% in the intervention groups compared to the control groups (RR+=0.87). Multifactorial (RR+=0.89) and education-based (RR=+0.84) interventions significantly reduced the probability of falls by 11% and 16%, respectively. CONCLUSIONS: Discarding publication bias prevention programs carried out by nurses produce a significant 10% reduction in falls. Education-based and multifactorial interventions are the most effective when conducted by nurses.

Changes in the saliva proteome analysed by gel-proteomics in horses diagnosed with equine gastric ulcer syndrome (EGUS) at diagnosis and after successful treatment.

Equine gastric ulcer syndrome (EGUS) is currently one of the more frequent diseases in horses. We aimed to identify changes in the salivary proteome in horses with EGUS at diagnosis and after successful treatment by using gel proteomics. Saliva samples were collected from nine horses with EGUS before and after treatment and nine matched healthy controls. SDS-PAGE (1DE) and two-dimensional gel electrophoresis (2DE) were performed, and significantly different protein bands and spots were identified by mass spectrometry. Horses with EGUS had increases in proteins such as adenosine deaminase (ADA), triosephosphate isomerase, keratins and immuno-globulin heavy constant mu and decreases in carbonic anhydrase (CA), albumin and prolactin-induced protein. These changes would indicate various physiopathological mechanisms involved in this disease, such as the activation of the immune system, decreased stomach defence mechanisms and inflammation. The treated horses presented lower expression levels of thioredoxin (TRX) after a successful treatment, in proteomics analysis and also measured with a commercially available ELISA kit. Overall, horses with EGUS have protein changes in their saliva when measured with gel proteomics compared with healthy horses, and they also showed changes after successful treatment. These proteins could be potential biomarkers for detection and monitoring treatment response in EGUS.

Natural history of renal angiomyolipoma in a high-volume center: our experience during more than 15 years of follow up.

OBJECTIVES: To describe the natural history of AML, the clinical results and the need for treatment during long-term follow-up of renal AML. METHODS: Retrospective study of patients diagnosed with AML by computed tomography or nuclear magnetic resonance between 2001 and 2019, with at least two follow-up images. Clinical and imaging variables, need for intervention, complications and follow-up time were recorded. Statistical analysis was performed using SPSS 22.0. RESULTS: 111 patients and 145 AML were included. The median follow-up was 6.17 years (range 0.7-18.1, IQR 11.8-12.2). The median tumor size at diagnosis was 13 mm (IQR 7.5-30), with 24 (16.4%) being ≥ 4 cm. Most presented as an incidental finding (85.5%); in 3 (2.1%) cases, the presentation was as a spontaneous retroperitoneal hematoma. The main indication for intervention was size ≥ 4 cm in 50%. Eighteen (12%) patients received a first intervention, being urgent in 3. Embolization was performed in 15 cases and partial nephrectomy in 3. The need for reintervention was recorded in five: two underwent partial nephrectomy and two total nephrectomy; one patient required a new urgent embolization. Of the non-operated patients, 43% decreased in size or did not change, while 57% increased, with the median annual growth being 0.13 mm (IQR - 0.11 to 0.73). There were no differences in the median growth in tumors measuring ≥ 4 cm (0.16 mm) at diagnosis vs. < 4 cm (0.13 mm) (p = 0.9). CONCLUSIONS: The findings of this study suggest that AML typically demonstrate a slow-progressing clinical course during long-term follow-up. Moreover, our observations, which cast doubt on tumor size as a reliable predictor of adverse clinical outcomes, advocate for a less intensive monitoring strategy in both monitoring frequency and choice of imaging modality.

Management of iron deficiency in women of childbearing age with oral iron intolerance: a prospective, randomised, controlled trial of three doses of an iron-whey-protein formulation : Prospective RandomisEd study of women of Childbearing age with gastroInteStinal Intolerance to Oral iroN (PRECISION).

BACKGROUND: Nutritional deficit and oral iron gastrointestinal intolerance may be a common cause of iron deficiency, which can be managed by pharmacists. AIM: To understand the prevalence of iron deficiency in women of childbearing age with a self-reported history of intolerance to oral iron and the tolerability of three doses of an iron-whey-protein formulation in the care of these women. METHOD: Ferritin and haemoglobin levels were documented in women of childbearing age with oral iron gastrointestinal intolerance. In those with iron deficiency (ferritin < 30 µg/L), adherence, gastrointestinal tolerability, ferritin, transferrin saturation and haemoglobin levels were compared between their prior oral iron product and iron-whey-protein microspheres randomised to three doses (14 mg daily, 25 mg daily and 50 mg daily) for 12 weeks. RESULTS: Most screened women had low iron stores (128 (62.7%); ferritin < 30 µg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin < 12 µg/L) and 33 (16.2%) had iron deficiency anaemia (ferritin < 30 µg/L, haemoglobin < 12 g/dL). Amongst the 59 women who participated in the prospective clinical study of iron-whey-protein microspheres over 12 weeks, 48 (81.4%) were classified as adherent/persistent and fewer instances of gastrointestinal intolerance were reported (0.59 ± 0.91) when compared to 12 (20.3%) and (4.0 ± 2.2) respectively while taking the prior oral iron (Fisher's Exact and T-test respectively, both p < 0.001). There was no difference in adherence or tolerability of different iron-whey-protein formulation doses. Ferritin, haemoglobin and energy levels increased significantly over 12 weeks. CONCLUSION: Undiagnosed iron deficiency is common in women of childbearing age with a history of intolerance to oral iron and iron-whey-protein microspheres can improve adherence, GI tolerability, iron stores, haemoglobin and energy levels in these women. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier (registration includes full trial protocol): NCT04778072.

Knowledge and Perceived Emotions Regarding an Anal Cancer Preventive Program in People Diagnosed With HIV: A Qualitative Study.

BACKGROUND: To the best of our knowledge, no studies have yet examined the emotional repercussions of the care processes among people infected with the human immunodeficiency virus who participate in preventive anal cancer screening programs. OBJECTIVE: This study aimed to explore the knowledge, emotions, sexuality, barriers, and facilitators perceived by this patient group during the process of anal cancer screening and diagnosis. METHODS: Detailed, semistructured, qualitative interviews were completed with 17 men and 3 women to explore their knowledge, experiences, and emotions regarding the screening process. Purposive sampling was conducted on the basis of age, gender, and type of lesion diagnosed in the anal biopsy. RESULTS: Four major themes were identified: 1) knowledge of the disease and its treatment, 2) emotions perceived by the patients, 3) the influence of screening on sexual practices, and 4) facilitators and obstacles during the care provision process. Patients reported appropriate knowledge of anal cancer and human papillomavirus. Predominant emotions were worry and fear with avoidance as one of the coping strategies. CONCLUSION: These results suggest that communication of information and clinical results can be improved. IMPLICATION FOR PRACTICE: Understanding the facilitators and barriers to the program will allow the integration of interventions designed to improve healthcare provision into direct care.

Influence of income on in-hospital mortality in older adults during the first wave of the COVID-19 pandemic: results from the EDEN-33 study. / Influencia de la renta económica en la mortalidad intrahospitalaria de las personas mayores durante la primera ola de la pandemia por COVID-19: resultados del estudio EDEN-33.

OBJECTIVES: To determine whether income was associated with unexpected in-hospital mortality in older patients treated in Spanish public health system hospital emergency departments. MATERIAL AND METHODS: Fifty-one public health system hospital emergency departments in Spain voluntarily participated in the study. Together the hospitals covered 25% of the population aged 65 years or older included in all patient registers during a week in the pre-pandemic period (April 1-7, 2019) and a week during the COVID-19 pandemic (March 30 to April 5, 2020). We estimated a patient's gross income as the amount published for the postal code of the patient's address. We then calculated the standardized gross income (SGI) by dividing the patient's estimated income by the mean for the corresponding territory (Spanish autonomous community). The existence and strength of an association between the SGI and in-hospital mortality was evaluated by means of restricted cubic spline (RCS) curves adjusted for 10 patient characteristics at baseline. Odds ratios (ORs) for each income level were expressed in relation to a reference SGI of 1 (the mean income for the corresponding autonomous community). We compared the COVID-19 and pre-pandemic periods by means of first-order interactions. RESULTS: Of the 35 280 patients attended in the 2 periods, gross income could be ascertained for 21 180 (60%), 15437 in the pre-pandemic period and 5746 during the COVID-19 period. SGIs were slightly higher for patients included before the pandemic (1.006 vs 0.994; P = .012). In-hospital mortality was 5.6% overall and higher during the pandemic (2.8% pre-pandemic vs 13.1% during COVID-19; P .001). The adjusted RCS curves showed that associations between income and mortality differed between the 2 periods (interaction P = .004). Whereas there were no significant income-influenced differences in mortality before the pandemic, mortality increased during the pandemic in the lowest-income population (SGI 0.5 OR, 1.82; 95% CI, 1.32-3.37) and in higher-income populations (SGI 1.5 OR, 1.32; 95% CI, 1.04-1.68, and SGI 2 OR, 1.92; 95% CI, 1.14-3.23). We found no significant differences between patients with COVID-19 and those with other diagnoses (interaction P = .667). CONCLUSION: The gross income of patients attended in Spanish public health system hospital emergency departments, estimated according to a patient's address and postal code, was associated with in-hospital mortality, which was higher for patients with the lowest and 2 higher income levels. The reasons for these associations might be different for each income level and should be investigated in the future.

OBJETIVO: Determinar si el nivel económico durante la primera ola pandémica tuvo una influencia diferente a la esperable en la mortalidad intrahospitalaria de los pacientes mayores atendidos en los servicios de urgencias (SU) de los hospitales públicos españoles. METODO: Cincuenta y un SU públicos españoles que participaron voluntariamente y que dan cobertura al 25% de la población incluyeron todos los registros de pacientes de edad 65 años atendidos durante una semana del periodo preCOVID (1-4-2019 a 7-4-2019) y una semana del periodo COVID (30-3-2020 a 5-4-2020). Se identificó la renta bruta (RB) asignada al código postal de residencia de cada paciente y se calculó la RB normalizada (RBN) dividiendo aquella por la RB media de su comunidad autónoma. La existencia y fuerza de la relación entre RBN y mortalidad intrahospitalaria se determinó mediante curvas spline cúbicas restringidas (SCR) ajustadas por 10 características basales del paciente. Las OR para cada situación económica se expresó en relación con una RBN de 1 (referencia, renta correspondiente a la media de la comunidad autónoma). La comparación entre periodo COVID y no COVID se realizó mediante el estudio de interacción de primer grado. RESULTADOS: De los 35.280 registros de pacientes atendidos en ambos periodos, se disponía de la RB en 21.180 (60%): 15.437 del periodo preCOVID y 5.746 del periodo COVID. La RBN de los pacientes incluidos fue discretamente superior en el periodo preCOVID (1,006 versus 0,994; p = 0,012). La mortalidad intrahospitalaria fue del 5,6%, y fue superior durante el periodo COVID (2,8% versus 13,1%; p 0,001). Las curvas SCR ajustadas mostraron una asociación entre nivel económico y mortalidad diferente entre ambos periodos (p interacción = 0,004): en el periodo preCOVID no hubo diferencias significativas de mortalidad en función de la RBN, mientras que en el periodo COVID la mortalidad se incrementó en rentas bajas (OR = 1,82, IC 95% = 1,32-3,37 para RBN de 0,5) y en rentas altas (OR = 1,32, IC 95% = 1,04-1,68 y OR = 1,92, IC 95% = 1,14-3,23 para RBN de 1,5 y 2, respectivamente), sin diferencias significativas entre pacientes con COVID y con otros diagnósticos (p interacción = 0,667). CONCLUSIONES: Durante la primera ola de la pandemia COVID, la RB asignada al código postal de residencia de los pacientes atendidos en los SU públicos españoles se asoció con la mortalidad intrahospitalaria, que aumentó en pacientes de rentas bajas y altas. Las razones de estas asociaciones pueden ser distintas para cada segmento económico y deben ser investigadas en el fututo.

Saliva Sampling Material Matters: Effects on the Results of Saliva Analysis in Pigs.

The use of saliva as a biological sample from pigs is of high practical interest because blood collection from pigs is difficult and stressful. In this study, the influence of two different materials, a cotton roll and a polypropylene sponge, in porcine saliva collection was evaluated. For this purpose, the effect of the material used for sampling was evaluated in a panel of 13 analytes, including those related to stress (cortisol and oxytocin), inflammation and immunity (adenosine deaminase, haptoglobin and myeloperoxidase), redox homeostasis (the cupric reducing ability of saliva, the ferric reducing activity of saliva, and the Trolox equivalent antioxidant capacity), and sepsis (procalcitonin), as well as other routine analytes related to metabolism and different tissues and organs, such as lactate dehydrogenase, creatine kinase, urea, and total protein concentration. The polypropylene sponge provided a higher sample volume than the cotton roll. Although the results of some salivary analytes were equivalent for both materials, other analytes, such as creatine kinase, haptoglobin and total proteins, showed significant differences depending on the material used for saliva collection. Therefore, the type of material used for salivary collection in pigs should be considered when interpreting the results of analyses of the salivary analytes.

Síndrome post COVID-19. Gravedad y evolución en 4673 trabajadores sanitarios / Post COVID-19 syndrome. Severity and evolution in 4673 health care workers

Resumen Introducción : La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos : Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados : Respondieron 4673 profesionales sanita rios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multi variado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al tra bajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión : En muchos casos la persistencia de los síntomas post COVID-19 puede ser prolongada y te ner un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.

Abstract Background : The evolution of post COVID-19 syn drome has been variable and we lack information on its impact on healthcare professionals. Methods : We conducted a survey through a social network in health professionals on post COVID-19 syn drome cases confirmed with PCR. In a web-based ques tionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. Results : 4673 health professionals from 21 countries responded, mean age of 47 years, 64% women. The initial course was asymptomatic in 9%, mild symptoms 36%, moderate symptoms without hospitalization 40% or with hospitalization 11%, and severe symptoms 1%. The most prevalent symptoms were fatigue (67%), insomnia (44%), anxiety (42%), myalgia (41%) and anosmia (41%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the mul 670 tivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7%, related to older age, number of symptoms and severity of the initial course. Conclusion : in many cases the persistence of post- COVID symptoms can be prolonged and have an occu pational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Bleeding and Thrombosis in Multiple Myeloma: Platelets as Key Players during Cell Interactions and Potential Use as Drug Delivery Systems.

Multiple myeloma (MM) is a hematological malignancy originated in the bone marrow and characterized by unhindered plasma cell proliferation that results in several clinical manifestations. Although the main role of blood platelets lies in hemostasis and thrombosis, platelets also play a pivotal role in a number of other pathological conditions. Platelets are the less-explored components from the tumor microenvironment in MM. Although some studies have recently revealed that MM cells have the ability to activate platelets even in the premalignant stage, this phenomenon has not been widely investigated in MM. Moreover, thrombocytopenia, along with bleeding, is commonly observed in those patients. In this review, we discuss the hemostatic disturbances observed in MM patients and the dynamic interaction between platelets and myeloma cells, along with present and future potential avenues for the use of platelets for diagnostic and therapeutic purposes.

Post COVID-19 syndrome. Severity and evolution in 4673 health care workers.

BACKGROUND: The evolution of post COVID syndrome has been variable and we lack information on its impact on healthcare professionals, particularly in Latin America. METHODS: We conducted a survey through a social network in health professionals on post COVID-19 syndrome cases confirmed with PCR. In a web-based questionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. RESULTS: 4673 health professionals from 21 countries responded, mean age of 47.8 years, 64.2% women. The initial course was asymptomatic in 9.1%, mild symptoms 36.8%, moderate symptoms without hospitalization 40.8% or with hospitalization 11.7%, and severe symptoms with respiratory assistance 1.6%. The most prevalent symptoms were fatigue (67%), insomnia (44.2%), anxiety (42.3%), myalgia (41.9%) and anosmia (41.2%). Considering only severe symptoms (grades 3-4 on a subjective index from 1 to 4), the most prevalent were slowness (36.3%), impaired concentration (33.1%), anosmia (20.4%), fatigue (19.1%), impaired memory (18.1%) and dyspnea (15.9%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the multivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7.8%, related to older age, number of symptoms and severity of the initial course. CONCLUSION: In conclusion, in many cases the persistence of post-COVID symptoms can be prolonged and have an occupational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Introducción: La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos: Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados: Respondieron 4673 profesionales sanitarios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multivariado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al trabajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión: En muchos casos la persistencia de los síntomas post-COVID puede ser prolongada y tener un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.

Could the IgA isotype provide additional information in systemic sclerosis patients? A retrospective study entailing IgA isotyping in a Mediterranean systemic sclerosis cohort.

OBJECTIVES: Anti-CENP-B (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (RP3) autoantibodies are included in the 2013 SSc-ACR/EULAR classification criteria. The detection of additional autoantibodies is of interest when those are negative. Additionally, we wonder if the IgA isotype might play a role in SSc. The aims of the study were to assess the prevalence of ACA, ATA, RP3, and Ro52 autoantibodies of IgG and IgA isotype and to describe their association with clinical manifestations in a cohort of patients with SSc. METHODS: Samples from 97 patients with SSc fulfilling the 2013 ACR/EULAR classification criteria, and 50 blood donors were included and tested for IgA and IgG isotypes of ACA, ATA, RP3, and Ro52 by FEIA. RESULTS: The prevalence of IgG+IgA isotypes for the same specificity was 62.5%, 82.6%, 80.0%, 36.8%, for ACA, ATA, RP3 and Ro52, respectively. Isolated IgG was present in 35.4%, 13.0%, 20.0% and 42.1% of patients for ACA, ATA, RP3 and Ro52, respectively. Only six patients were isolated IgA for a unique specificity. Clinically, ILD tended to be associated with ATA-IgG and ATA-IgG+IgA, telangiectasias with ACA-IgG+IgA and arthritis with ACA-IgA. Indeed, digital ulcers were more frequent in ATA-IgG patients. CONCLUSIONS: Most of the patients presented ACA, ATA, or RP3 autoantibodies of IgA isotype in addition to IgG. Regarding clinical relevance, Ro52-IgG+IgA and ACA-IgG had a tendency towards sineSSc phenotype, while ACA-IgG+IgA to lcSSc phenotype. Thus, if confirmed, the determination of ACA-IgA could provide a tool to stratify patients according to the cutaneous phenotype.

Changes in S100A8/A9 and S100A12 and Their Comparison with Other Analytes in the Saliva of Pigs with Diarrhea Due to E. coli.

The family of calgranulins includes S100A8 (calgranulin A), S100A9 (calgranulin B), which can appear as a heterodimer known as S100A8/A9 or calprotectin, and S100A12 (calgranulin C). These proteins are related to different inflammatory conditions, immune-mediated diseases, and sepsis and are considered biomarkers of potential interest. This study aims to evaluate if S100A8/A9 and A12 could change in pigs with diarrhea due to E. coli and to compare the changes of S100A8/A9 and A12 with other analytes in order to explore the possible causes or mechanisms involved. For this purpose, a panel integrated by analytes related to inflammation (haptoglobin, inter-alpha trypsin inhibitor 4 (ITIH4), and total protein); immune system (adenosine deaminase, ADA); stress (alpha-amylase); tissue damage (lactate and lactate dehydrogenase (LDH)); sepsis (aldolase) and redox status (ferric-reducing ability of saliva (FRAS) and advanced oxidation protein products (AOPP)) was evaluated. S100A8/A9 and A12 and the other analytes measured in this study showed increases in the saliva of pigs with diarrhea due to E. coli. S100A8/A9 and/or A12 showed a significant correlation of different magnitude with some of the other analytes evaluated. Further studies should be conducted to gain knowledge about the possible practical applications as biomarkers of the measurements of S100A8/A9 and A12 in the saliva of pigs.

Evaluation of the validity of the HPV viral load compared to conventional techniques for the detection of high-grade anal intraepithelial lesions in men with HIV who have sex with men.

Background: The incidence of high-grade anal intraepithelial lesions (HSILs) has increased in recent years among men who have sex with men with human immunodeficiency virus (HIV). This work evaluated the validity of the human papilloma virus viral load (HPV-VL) versus cytological and qualitative HPV results to detect HSILs. Methods: From May 2017 to January 2020, 93 men who have sex with men and HIV were included in an anal cancer screening program from the Infectious Diseases Unit at a tertiary-care hospital in Alicante (Spain). The gold-standard for the screening of anal HSILs is the anal biopsy using high-resolution anoscopy. The diagnostic methods compared against gold-standard were HPV-16-VL, HPV-18-VL, and HPV-16-18-VL co-testing, anal cytology, and qualitative HPV detection. The receiver operating characteristic (ROC) curve and cut-off points for HPV-VL were calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's Kappa coefficient (κ) were also calculated. Results: The mean patient age was 44.6 ± 9.5 years. All of them received antiretroviral treatment, 96.8% had an HIV viral load of <50 copies/mL and 17.2% had a previous diagnosis of AIDS. The diagnosis of the anal biopsies were: 19.4% (n = 18) HSIL, 29.1% (n = 27) LSIL, and 51.6% (n = 48) negative. An HPV-16-VL >6.2 copies/cell was detected in the HSIL biopsy samples (p = 0.007), showing a sensitivity of 100% and a specificity of 46.2%. HPV-18-VL and HPV16-18-VL co-testing showed a sensitivity of 75% and 76.9% and a specificity of 72.7% and 61.3%, respectively. The highest PPV was 50% obtained with the cytology and HPV-18-VL. The HPV-16-VL showed a NPV of 100%, followed by 88.9% in the HPV-18-VL and 87% in the abnormal cytology. Cohen's Kappa coefficient were: HPV-18-VL (κ = 0.412), abnormal cytology (κ = 0.353) and HPV-16-VL (κ = 0.338). Conclusions: HPV-VL testing improved the detection sensitivity but not the specificity for HSIL biopsies compared to anal cytology and the qualitative detection of HPV. In men who have sex with men and HIV the HPV-VL could be an useful tool for diagnosis of HSILs in anal cancer screening programs. Further studies will be needed to evaluate the clinical implications of HPV-VL in these programs.

Analysing biomarkers in oral fluid from pigs: influence of collection strategy and age of the pig.

BACKGROUND AND OBJECTIVES: Oral fluid (OF) is an easy-to-collect, inexpensive, fast and non-invasive sample to characterize health and welfare status of the pig. However, further standardisation of the collection methods is needed in order to use it regularly in veterinary practice. Cotton ropes are routinely used to collect OF for pathogen detection but they may not be optimal for biomarker analysis due to sample contamination. This study compared two methods (cotton ropes and sponges) to collect porcine OF for biomarker analysis. A panel of 11 biomarkers of stress, inflammation, sepsis, immunity, redox status and general homeostasis was studied. MATERIALS AND METHODS: Eighteen farrow-to-finish pig farms were included in the study. In each farm, three (for sponges) or four pens of pigs (for ropes) were sampled at four age categories: the week after weaning (5 weeks), before (11-12 weeks) and after (12-13 weeks) moving to finisher facility and the week before slaughter (22-25 weeks). In total, 288 OF samples were collected with cotton ropes and 216 with sponges and analysed for the biomarkers: cortisol, alpha-amylase, oxytocin (stress), haptoglobin (inflammation), procalcitonin (sepsis), adenosine deaminase, immunoglobulin G (immune system), ferric reducing antioxidant power (redox status), and creatine kinase, lactate dehydrogenase and total protein (general homeostasis). Samples were also scored visually for dirtiness using a score from 1 (clean) to 5 (very dirty). RESULTS: Rope-collected OF had higher levels of dirtiness (3.7 ± 0.04) compared to sponge-collected OF (2.7 ± 0.15) and had higher values than sponges for cortisol, procalcitonin, oxytocin, haptoglobin, total protein, lactate dehydrogenase and ferric reducing antioxidant power. All biomarkers decreased in value with age. Immunoglobulin G did not perform well for any of the two collection methods. DISCUSSION AND CONCLUSION: The results showed a clear effect of age on the biomarkers in OF collected with both, sponges or ropes. Sponges provided a cleaner sample than cotton ropes for biomarker analysis. Both methods are easy to apply under the commercial conditions in pig farms although sponges may take more time in early weaner stages. From a practical point of view, sampling with sponges achieved the best combination of reduced sampling time and low contamination.

Changes in salivary biomarkers of stress, inflammation, redox status, and muscle damage due to Streptococcus suis infection in pigs.

BACKGROUND: Streptococcus suis (S. suis) is a Gram-positive bacteria that infects pigs causing meningitis, arthritis, pneumonia, or endocarditis. This increases the mortality in pig farms deriving in severe economic losses. The use of saliva as a diagnostic fluid has various advantages compared to blood, especially in pigs. In this study, it was hypothesized that saliva could reflect changes in different biomarkers related to stress, inflammation, redox status, and muscle damage in pigs with S. suis infection and that changes in these biomarkers could be related to the severity of the disease. RESULTS: A total of 56 growing pigs from a farm were selected as infected pigs (n = 28) and healthy pigs (n = 28). Results showed increases in biomarkers related to stress (alpha-amylase and oxytocin), inflammation (haptoglobin, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), total protein, S100A8-A9 and S100A12), redox status (advanced oxidation protein producs (AOPP)) and muscle damage (creatine kinase (CK), CK-MB, troponin I, lactate, aspartate aminotransferase, and lactate dehydrogenase). An increase in adenosine deaminase (ADA), procalcitonin, and aldolase in infected animals were also observed, as previously described. The grade of severity of the disease indicated a significant positive correlation with total protein concentrations, aspartate aminotransferase, aldolase, and AOPP. CONCLUSIONS: This report revealed that S. suis infection caused variations in analytes related to stress, inflammation, redox status, and muscle damage in the saliva of pigs and these can be considered potential biomarkers for this disease.