Prevalence and sociodemographic correlates of antinuclear antibody testing by indirect immunofluorescence or solid-phase assays in a Spanish population: the Camargo Cohort.

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

A Delphi consensus on the management of Spanish patients with osteoporosis at high risk of fracture: OSARIDELPHI study.

The OSARIDELPHI study evaluated the level of agreement between specialists in osteoporosis regarding the management of patients with high-risk fractures in Spain. The results provide expert-based recommendations for prevention, diagnosis, and treatment related to fracture risk. Therefore, the study facilitates clinical decision-making for managing this patient's profile. PURPOSE: To evaluate the level of agreement between specialists in osteoporosis regarding the management of patients with high-risk fractures in Spain. METHODS: A two-round Delphi study was performed using an online survey. In round 1, panel members rated their level of agreement with assessments on a 9-point Likert scale. Item selection was based on acceptance by ≥ 66.6% of panel experts and the agreement of the scientific committee. In round 2, the same panelists evaluated non-consensus items in round 1. RESULTS: A total of 80 panelists participated in round 1; of these, 78 completed the round 2 survey. In round 1, 122 items from 4 dimensions (definition of fracture risk: 11 items, prevention and diagnosis: 38 items, choice of treatment: 24 items, and treatment-associated quality of life: 49 items) were evaluated. The consensus was reached for 90 items (73.8%). Panelists agreed that categorizing high risk, very high risk, or imminent risk determines secondary prevention actions (97.5%). Experts agreed that treatment with bone-forming drugs should be considered in case of a very high risk of fracture, and a sequential change to antiresorptive drugs should be made after 1-2 years (97.5%). Panelists also recommended corrective action plans for non-adherent patients to improve adherence (97.5%). A total of 131 items were finally accepted after round 2. CONCLUSION: This Delphi study provides expert-based recommendations on clinical decision-making for managing patients with osteoporosis at high risk of fracture.

Influence of non-osteoporotic treatments in patients on active anti-osteoporotic therapy: evidence from the OSTEOMED registry.

PURPOSE: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. METHODS: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. RESULTS: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). CONCLUSION: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide.

Genistein supplementation has no effects on vitamin D levels in healthy Spanish postmenopausal women.

Background: In vitro studies have shown that genistein inhibits the CYP240 enzyme, which is involved in the degradation of 1,25-dihydroxycholecalciferol and its precursor 25-hydroxycholecalciferol, and increases their plasma levels. However, no clinical studies have primarily assessed the synergistic effect of isoflavones on vitamin D levels. The aim of this study was to evaluate the possible additive effect of genistein supplementation on vitamin D levels, calcium metabolism and bone remodeling markers in healthy postmenopausal women during the spring-summer months. Patients and methods: We made a prospective, double-blind study with 150 healthy postmenopausal women that were randomized to three groups. One received placebo, another received calcium (1000 mg/day) and vitamin D (cholecalciferol, 800 U/day) and the third received calcium (1000 mg/day), vitamin D (cholecalciferol, 800 U/day) and genistein (90 mg/day). The study period was from May to September (spring-summer). Vitamin D, PTH, CTX and P1NP were determined by electrochemiluminescence at baseline and after 12 weeks. Results: Vitamin D levels increased in all groups: placebo (23±9 ng/ml vs. 29±10 ng/ml, p<0.05), calcium+vitamin D (26±10 ng/ml vs. 33±8 ng/ml, p<0.05) and calcium+vitamin D+genistein (24±9 ng/ml vs. 31±8 ng/l, p<0.05) without between-group differences. At study end, the percentage of women with vitamin D <20 ng/ml (11%) and <30 ng/ml (39%) had fallen without between-group differences. The effects on calcium metabolism and bone remodeling markers were similar between groups: rises in vitamin D were significantly linked to reductions in PTH, CTX and P1NP. Conclusion: Adding genistein to supplementation with calcium and vitamin D provided not additional changes in vitamin D levels, calcium metabolism or bone remodeling markers in healthy Spanish postmenopausal women during the spring-summer months.

Serum alpha-CGRP levels are increased in COVID-19 patients with headache indicating an activation of the trigeminal system.

BACKGROUND: Headache is among the most frequent symptoms of acute COVID-19 infection. Its mechanisms remain obscure, but due to its migraine-like characteristics, the activation of the trigeminal system could account for its underlying pathophysiology. METHODS: Our aim was to compare the serum levels of CGRP, as a theoretical marker of trigemino-vascular activation, in 25 COVID-19 inpatients with lung involvement experiencing headache, against 15 COVID-19 inpatients without headache and with those of 25 matched healthy controls with no headache history. RESULTS: Morning serum alpha-CGRP levels, as measured by ELISA (Abbexa, UK), were increased in COVID-19 patients with headache (55.2±34.3 pg/mL) vs. controls (33.9±14.0 pg/mL) (p < 0.01). Alpha-CGRP levels in COVID-19 patients without headache were also significantly increased (43.3 ± 12.8 pg/mL; p = 0.05) versus healthy controls, but were numerically lower (-28.2%; p = 0.36) as compared to COVID-19 patients with headache. CONCLUSION: CGRP levels are increased in COVID-19 patients experiencing headache in the acute phase of this disease, which could explain why headache frequently occurs in COVID-19 and strongly supports a role for trigeminal activation in the pathophysiology of headache in this viral infection.

Serum Calcitonin Gene-Related Peptide α and ß Levels are Increased in COVID-19 Inpatients.

BACKGROUND: Vasoactive peptides play an important role in a wide range of physiological and pathological conditions. Due to its known functions, the calcitonin gene-related peptide (CGRP) has been suggested as a possible modulator of the hyperimmune response in COVID-19 and thus, blocking its action may lessen the pulmonary effects of COVID-19. AIM OF THE STUDY: To compare the circulating levels of CGRPα and CGRPß in healthy controls compared to hospitalized COVID-19 patients. The study also analyzed how different comorbidities and treatments may affect these concentrations in cases of COVID-19 infection with pulmonary involvement METHODS: Serum samples were collected from the antecubital vein of 51 control subjects (mean age = 55 ± 14 years; range = 26-77; 56.9% female) and 52 patients hospitalized with COVID-19 infection (mean age = 55 ± 13; range = 23-77; 55.8% female) from December 2020 to May 2021. Enzyme-linked immunosorbent assays (ELISAs) were used for CGRPα (Abbexa, UK) and CGRPß (CUSABIO, China) measurements. Comorbidities, symptoms, and treatments of infection were listed. RESULTS: The results showed that the serum levels of both isoforms of CGRP were significantly higher in patients with COVID-19 (α: 57.9 ± 35.8 pg/mL; ß: 6.1 ± 2.6 pg/mL) compared to controls (α: 41.8 ± 25.4 pg/mL; ß: 4.5 ± 2.4 pg/mL) (p <0.01). Also, the presence of arterial hypertension (HT), obesity, or corticosteroid treatment significantly alter the serum concentration of CGRPα in the subgroups compared to controls. CONCLUSION: The elevated serum CGRP levels found in our COVID-19 group compared to controls may suggest that CGRP plays a role in the pathophysiology of the disease, more specifically, in the cytokine storm and in the pulmonary involvement. Future studies should focus on the source of this CGRP elevation.

Comparison of ANA testing by indirect immunofluorescence or solid-phase assays in a low pre-test probability population for systemic autoimmune disease: the Camargo Cohort.

OBJECTIVES: Autoantibodies and, specifically antinuclear antibodies (ANA), are the hallmark of systemic autoimmune diseases (AID). In the last decades, there has been great technical development to detect these autoantibodies along with an increased request for this test by clinicians, while the overall pre-test probability has decreased. In this study, we compare the diagnostic performance of three different methods for ANA screening (indirect immunofluorescence [IIF], addressable laser bead immunoassay [ALBIA], and fluorescence enzyme immunoassay [FEIA]). METHODS: Serum samples at baseline visit from 2,997 participants from the Camargo Cohort, a population with an overall low pre-test probability for systemic AID, were analyzed with the three methods. Participants have a minimum follow-up of 10 years and the development of autoimmune diseases was collected from clinical records. RESULTS: The highest frequency of positive ANA was observed by IIF assay. However, ALBIA showed high sensitivity for AID. Likewise, solid phase assays (SPA) presented higher specificity than IIF for AID. ANA prevalence with any method was significantly higher in females and overall increased with age. Triple positivity for ANA was significantly related to the presence of anti-dsDNA-SSA/Ro60, Ro52, SSB/La, RNP, Scl-70, and centromere-specificities. No association was found for anti-Sm - RNP68, or ribosomal P - specificities. Noteworthy, triple positivity for ANA screening was associated with diagnosis of systemic AID both at baseline visit and follow-up. CONCLUSIONS: ANA detection by IIF may be better when the pre-test probability is high, whereas SPA techniques are more useful in populations with an overall low pre-test probability for systemic AID.

Post grafted gallic acid to chitosan-Ag hybrid nanoparticles via free radical-induced grafting reactions.

The present study proposes two unique systems using free radical-induced grafting reactions to combine Ag, chitosan (CS) and gallic acid (GA) into a single particulate nanostructure. GA-grafted-CS (GA-g-CS) was used to reduce Ag+ to Ag0, and producing Ag-GA-g-CSNPs (hybrid NPs I). Also, GA was grafted into CS-AgNPs, to form GA-g-CS AgNPs (hybrid NPs II). Although there were previous attempts to graft GA into CS, this is first time to graft GA into CS-AgNPs. The study aimed to enhance biocompatibility, antibacterial and antioxidant properties of CS-AgNPs via grafted GA. Grafting GA into CS-AgNPs was confirmed by UV-Vis, DLS, DSC/TGA, XRD, EDX and FTIR. The morphology and size of NPs were studied by TEM and SEM. The decrease of ζ-potential from +50 mV in CS-Ag NPs to +33 and + 29 mV, in the presented 2 nanoforms hybrid NPs I and II, respectively, is an indication for the successful GA graft. Among all samples, hybrid NPs II showed lower toxicity, higher antioxidant and antibacterial activity. The obtained results revealed that grafting GA to CS-AgNPs, as a new method to combine Ag, CS and GA in a uniparticulate structure, is a unique process which may deserve a more future consideration.

High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study.

OBJECTIVES: To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture. METHODS: Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients. RESULTS: Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37). CONCLUSION: Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development.

Bone Metabolism in Patients with Hidradenitis Suppurativa: A Case-control Study.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicles. The aim of this case-control study was to assess whether HS is associated with disturbances in trabecular bone score, bone mineral density, bone remodelling markers, and calciotropic hormones. A total of 81 patients and 79 controls of similar age and sex were included. Demographic, anthropometric, laboratory data, trabecular bone score, bone mineral density, serum 25-hydroxyvitamin D (25OHD), serum amino-terminal pro-peptide of type 1 collagen (PINP), and C-terminal telopeptide of type 1 collagen (CTX) concentrations were assessed in both groups. Patients with HS had lower serum 25OHD levels than controls, and approximately 62% of them had vitamin D deficiency. Serum PINP was increased and CTX was decreased in patients with HS. Fully adjusted trabecular bone score values were lower in patients with HS compared with controls. Adjusted lumbar bone mineral density was similar in HS and controls, whilst total hip bone mineral density was lower in patients with HS. There were no statistical differences regarding disease severity in terms of 25OHD, serum turnover markers, bone mineral density, or trabecular bone score values. This study shows that patients with HS have lower trabecular bone score and total hip bone mineral density values than population-based controls. In addition, the prevalence of vitamin D deficiency is high in subjects with HS.

Blood group O is associated with post-COVID-19 syndrome in outpatients with a low comorbidity index.

BACKGROUND: ABO blood group system modulates the inflammatory response and has been implicated in COVID-19. Group O protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association. METHODS: Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, group O. We collected age, sex, BMI, smoking, comorbidities, inflammatory markers, anti-SARS-CoV-2 IgG antibodies, blood type and clinical data. Five composite inflammatory indices were developed. Multivariate analyses were performed. RESULTS: We analysed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 41.5%, 7.9%, 5.9%, and 44.5% for A, B, AB and O, respectively. Thirty-six patients were PCS+, without significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (p = .036), and number of symptoms of PCS (p = .017) were noted in group O. Concerning biomarkers, PCS + and PCS- showed no differences in A, B, and AB groups. In contrast, group O PCS + patients had significantly lower albumin-to-globulin ratio and higher lymphocyte count, fibrinogen, CRP levels, and higher percentages of 3 composite indices, than PCS- subjects. Group O showed a 6-fold increased risk of PCS, compared to non-O (adjusted OR = 6.25 [95%CI, 1.6-23]; p = .007). CONCLUSIONS: Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.

Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry.

PURPOSE: To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients. METHODS: For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model. RESULTS: Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer-Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6). CONCLUSION: In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit.

Impact of the SARS-CoV-2 pandemic on pancreatic cancer: diagnosis and short-term survival.

INTRODUCTION: The COVID-19 pandemic has delayed medical consultation, possibly leading to the diagnosis of gastrointestinal cancer. The aim of the study was to analyze the impact of SARS-Cov-2 pandemic on new diagnosis and short-term survival of patients with pancreatic cancer (PC). METHODS: All consecutive patients who had a suspected diagnosis of pancreatic lesion before (from March to September 2019) and during COVID 19 pandemic (from March to September 2020). Demographics, clinical and treatment were collected and compared. Short-term survival was assessed. RESULTS: A total of 25 patients (n=13 men) with diagnosis of adenocarcinoma of the pancreas and a median age of 70 years (IQR 62-74) were included. An increase was observed in the number of patients with newly diagnosed PC (n= 12 [19.1%] versus n=13 [20.9%]; P= 0.603). The subgroup analysis revealed a tendency toward a longer diagnosis (11 versus 12 days; P= 0.219) and treatment (28 versus 44; P= 0.375) delay for patients with PC during COVID-19 pandemic. A significant increase was observed for number of cases of advanced stage III and IV (n=4 [30.8%] versus n=7 [53.8%]; P= 0.006). Palliative treatment was the most frequent approach during COVID-19 period. During 1-year follow-up, 6 (50%) and 7 (61.5%) deaths were observed among patients diagnosed before and after COVID-19 (P= 0.449), respectively. CONCLUSIONS: The COVID-19 pandemic has led to delays in diagnosis and treatment in PC, which translates into an advanced staging and a worse prognosis. These data should stimulate health care provider to facilitate procedures for detection pancreatic cancer.

Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients.

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8+CD38+HLADR+ and CD8+CD27-CD28-, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8+CD27-CD28-, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease.

3D analysis of bone mineral density in a cohort: age- and sex-related differences.

Women have lower areal BMD (g/cm2) than men; however, the women have smaller-size bones. Our study showed that women ≤ 59 years have a hip volumetric BMD by DXA 3D similar to that of men of the same age. This makes us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass. PURPOSE: Women have lower areal BMD (g/cm2) than men; however, these studies do not take into account that women have smaller-size bones. Recently, three-dimensional (3D) modeling methods were proposed to analyze volumetric BMD (vBMD). We want to determine the values of vBMD at the hip by DXA-based 3D modeling in a cohort of people in order to know the age- and sex-related differences. METHODS: A total of 2647 people of both sexes (65% women) were recruited from a large cohort (Camargo cohort, Santander, Spain). 3D-SHAPER® software (version 2.8, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from the hip DXA scans at baseline RESULTS: The differences were less pronounced for vBMD (cortical sBMD 9.3%, trabecular vBMD 6.4%, integral vBMD 2.2%) compared to aBMD (FN aBMD 11.4% and TH aBMD 13.3%). After stratifying by age (≤ 59 years, 60-69 years, 70-79 years, and ≥ 80 years), we observed in ≤ 59 years that aBMD was lower in women compared to men, at FN (0.758 [0.114] g/cm2 vs. 0.833 [0.117] g/cm2; p = 1.4 × 10-20) and TH (0.878 [0.117] g/cm2 vs. 0.990 [0.119] g/cm2; p = 4.1 × 10-40). Nevertheless, no statistically significant difference was observed for integral vBMD (331 [58] mg/cm3 in women and 326 [51] mg/cm3 in men; p = 0.19) and trabecular vBMD (190 [41] mg/cm3 in women and 195 [39] mg/cm3 in men; p = 0.20). CONCLUSION: Our results make us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass.

Usefulness of the COVID-GRAM and CURB-65 scores for predicting severity in patients with COVID-19.

AIM: The aim of this study was to determine the usefulness of COVID-GRAM and CURB-65 scores as predictors of the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Caucasian patients. METHODS: This was a retrospective observational study including all adults with SARS-CoV-2 infection admitted to Hospital Universitario Marqués de Valdecilla from February to May 2020. Patients were stratified according to COVID-GRAM and CURB-65 scores as being at low-medium or high risk of critical illness. Univariate analysis, multivariate logistic regression models, receiver operating characteristic curve, and area under the curve (AUC) were calculated. RESULTS: A total of 523 patients were included (51.8% male, 48.2% female; mean age 65.63 years (standard deviation 17.89 years)), of whom 110 (21%) presented a critical illness (intensive care unit admission 10.3%, 30-day mortality 13.8%). According to the COVID-GRAM score, 122 (23.33%) patients were classified as high risk; 197 (37.7%) presented a CURB-65 score ≥2. A significantly greater proportion of patients with critical illness had a high COVID-GRAM score (64.5% vs 30.5%; P < 0.001). The COVID-GRAM score emerged as an independent predictor of critical illness (odds ratio 9.40, 95% confidence interval 5.51-16.04; P < 0.001), with an AUC of 0.779. A high COVID-GRAM score showed an AUC of 0.88 for the prediction of 30-day mortality, while a CURB-65 ≥2 showed an AUC of 0.83. CONCLUSIONS: The COVID-GRAM score may be a useful tool for evaluating the risk of critical illness in Caucasian patients with SARS-CoV-2 infection. The CURB-65 score could be considered as an alternative.

Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial.

BACKGROUND: SARS-CoV-2 infection presents a high transmission in the group of health professionals in Spain (12-15% infected). Currently there is no accepted chemoprophylaxis but hydroxychloroquine (HDQ) is known to inhibit the coronavirus in vitro. Our hypothesis is that oral administration of hydroxychloroquine to healthcare professionals can reduce the incidence and prevalence of infection as well as its severity in this group. METHODS: Design: Prospective, single center, double blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult health-care professionals (18-65 years) working in areas of high exposure and high risk of transmission of SARS-COV-2 (COVID areas, Intensive Care Unit -ICUs-, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. Exclusion criteria include previous infection with SARS CoV2 (positive SARS-CoV-2 PCR or IgG serology), pregnancy or lactation, any contraindication to hydroxychloroquine or evidence of unstable or clinically significant systemic disease. INTERVENTIONS: Patients will be randomized (1:1) to receive once-daily oral Hydroxychloroquine 200mg for two months (HC group) or placebo (P group) in addition to the protective measures appropriate to the level of exposure established by the hospital. A serological evaluation will be carried out every 15 days with PCR in case of seroconversion, symptoms or risk exposure. Primary outcome is the percentage of subjects presenting infection (seroconversion and/or PCR +ve) by the SARS-Cov-2 virus during the observation period. Additionally, both the percentage of subjects in each group presenting Pneumonia with severity criteria (Curb 65 ≥2) and that of subjects requiring admission to ICU will be determined. DISCUSSION: While awaiting a vaccine, hygiene measures, social distancing and personal protective equipment are the only primary prophylaxis measures against SARS-CoV-2, but they have not been sufficient to protect our healthcare professionals. Some evidence of the in vitro efficacy of hydroxychloroquine against this virus is known, along with some clinical data that would support the study of this drug in the chemoprophylaxis of infection. However, there are still no data from controlled clinical trials in this regard. If our hypothesis is confirmed, hydroxychloroquine can help professionals fight this infection with more guarantees. PARTICIPANTS: This is a single-center study that will be carried out at the Marqués de Valdecilla University Hospital. 450 health professionals working at the Hospital Universitario Marqués de Valdecilla in areas of high exposure and high risk of transmission of SARS COV2 (COVID hospital areas, Intensive Care Unit, Emergency, Anesthesia and all those performing aerosol-generating procedures) will be included. INCLUSION CRITERIA: 1) Health professionals aged between 18 and 65 years (inclusive) at the time of the first screening visit; 2) They must provide signed written informed consent and agree to comply with the study protocol; 3) Active work in high exposure areas during the last two weeks and during the following weeks. EXCLUSION CRITERIA: 1) Previous infection with SARS CoV2 (positive coronavirus PCR or positive serology with SARS Cov2 negative PCR and absence of symptoms); 2) Current treatment with hydroxychloroquine or chloroquine; 3) Hypersensitivity, allergy or any contraindication for taking hydroxychloroquine, in the technical sheet; 4) Previous or current treatment with tamoxifen or raloxifene; 5) Previous eye disease, especially maculopathy; 6) Known heart failure (Grade III to IV of the New York Heart Association classification) or prolonged QTc; 7) Any type of cancer (except basal cell) in the last 5 years; 6) Refusal to give informed consent; 8) Evidence of any other unstable or clinically significant untreated immune, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric illness; 9) Antibodies positive for the human immunodeficiency virus; 10) Significant kidney or liver disease; 11) Pregnancy or lactation. INTERVENTION AND COMPARATOR: Two groups will be analyzed with a 1: 1 randomization rate. 1)Intervention: (n = 225): One 200 mg hydroxychloroquine sulfate coated tablet once daily for two months.2)Comparator (control group) (n = 225): One hydroxychloroquine placebo tablet (identical to that of the drug) once daily for two months MAIN OUTCOMES: The primary outcome of this study will be to evaluate: number and percentage of healthcare personnel presenting symptomatic and asymptomatic infection (see "Diagnosis of SARS CoV2 infection" below) by the SARS-Cov2 virus during the study observation period (8 weeks) in both treatment arms;number and percentage of healthcare personnel in each group presenting with Pneumonia with severity criteria (Curb 65 ≥2) and number and percentage of healthcare personnel requiring admission to the Intensive Care Unit (ICU) in both treatment arms. DIAGNOSIS OF SARS COV2 INFECTION: Determination of IgA, IgM and IgG type antibodies against SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA kit (EUROIMMUN Medizinische Labordiagnostika AG, Germany) every two weeks. In cases of seroconversion, a SARS-CoV-2 PCR will be performed to rule out / confirm an active infection (RT-PCR in One Step: RT performed with mastermix (Takara) and IDT probes, following protocol published and validated by the CDC Evaluation of COVID-19 in case of SARS-CoV-2 infection RANDOMISATION: Participants will be allocated to intervention and comparator groups according to a balanced randomization scheme (1: 1). The assignment will be made through a computer-generated numeric sequence for all participants BLINDING (MASKING): Both participants and investigators responsible for recruiting and monitoring participants will be blind to the assigned arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Taking into account the current high prevalence of infection in healthcare personnel in Spain (up to 15%), to detect a difference equal to or greater than 8% in the percentage estimates through a two-tailed 95% CI, with a statistical power of 80% and a dropout rate of 5%, a total of 450 participants will need to be included (250 in each arm). TRIAL STATUS: The protocol approved by the health authorities in Spain (Spanish Agency for Medicines and Health Products "AEMPS") and the Ethics and Research Committee of Cantabria (CEIm Cantabria) corresponds to version 1.1 of April 2, 2020. Currently, recruitment has not yet started, with the start scheduled for the second week of May 2020. TRIAL REGISTRATION: Eudra CT number: 2020-001704-42 (Registered on 29 March 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Revisión de la evidencia sobre el manejo de medicamentos y productos peligrosos en los servicios de Urología; documento de consenso entre la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria / Review of evidence on handling hazardous drugs and Products in Urology Services; consensus document between the Spanish Urology Association and the Spanish Society of Health-System Pharmacists

Objetivo: La administración intravesical de medicamentos peligrosos es una práctica habitual en el ámbito de la urología, con posible exposición del personal sanitario a dichos medicamentos. Se considera necesario disponer de un documento de consenso entre las sociedades científicas implicadas -Asociación Española de Urología y Sociedad Española de Farmacia Hospitalaria- que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible, de medicamentos peligrosos en el ámbito de los servicios de Urología. Método: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional. Resultados: Se dispone de legislación nacional y de normativas para la protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores

Objective: The intravesical administration of hazardous drug products is a standard practice in the urology setting, which potentially exposing medical personnel to these drug products. It was deemed necessary to have a consensus document among the scientific societies involved (the Spanish Urological Association and the Spanish Society of Hospital Pharmacy) that collects the best available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. Method: We reviewed the legislation and recommendations on the handling of dangerous drug products, both at the national and international level. Results: There is national legislation and regulations for protecting workers who handle dangerous drugs and products, as well as recommendations for handling to protect both the product and workers

Review of evidence on handling hazardous drugs and Products in Urology Services; consensus document between the Spanish Urology Association and the Spanish Society of Health-System Pharmacists.

OBJECTIVE: The intravesical administration of hazardous drug products is a  standard practice in the urology setting, which potentially exposing medical  personnel to these drug products. It was deemed necessary to have a consensus document among the scientific societies involved (the Spanish Urological  Association and the Spanish Society of Hospital Pharmacy) that collects the best  available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. METHOD: We reviewed the legislation and recommendations on the handling of  dangerous drug products, both at the national and international level. RESULTS: There is national legislation and regulations for protecting workers who  handle dangerous drugs and products, as well as  recommendations for handling to protect both the product and workers. DISCUSSION: Following the strategic lines of the European Parliament for 2014- 2020 in the chapter on occupational safety and health, the Spanish Urological  Association and the Spanish Society of Hospital Pharmacy proposed a series of  actions that decrease the risks of exposure for practitioners and caregivers  involved in the handling of these products. CONCLUSIONS: After this review, 19 recommendations were established for  handling dangerous drug products, which can be summarised as the need to  train all individuals involved (from management teams to patients and  caregivers), adopt systems that prevent contaminating leaks, implement  exposure surveillance programmes and optimise available resources.

Objetivo: La administración intravesical de medicamentos peligrosos es una  práctica habitual en el ámbito de la urología, con posible exposición del personal  sanitario a dichos medicamentos. Se considera necesario disponer de un  documento de consenso entre las sociedades científicas implicadas ­Asociación  Española de Urología y Sociedad Española de Farmacia Hospitalaria­ que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible,  de medicamentos peligrosos en el ámbito de los servicios de Urología.Método: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional.Resultados: Se dispone de legislación nacional y de normativas para la  protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores.Discusión: Siguiendo las líneas estratégicas del Parlamento Europeo para el  período 2014-2020 en el capítulo de seguridad y salud laboral, la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria proponen una serie de actuaciones que hagan disminuir los riesgos de exposición de los profesionales y cuidadores implicados en su manejo. Conclusiones: Tras esta revisión se establecen 19 recomendaciones para el  manejo de medicamentos peligrosos que pueden resumirse en la necesidad de  formación de todas las personas implicadas (desde los equipos directivos hasta  los pacientes y cuidadores), la adopción de sistemas que no permitan fugas  contaminantes, programas de vigilancia de las exposiciones y optimización de  los recursos disponibles.