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.

Speech therapy and hyperbaric oxygen for aphasia after carbon monoxide intoxication.

Acute carbon monoxide (CO) intoxication may result in delayed neurological sequelae, which can include amnesia, ataxia, aphasia, emotional lability, disorientation, dysphagia, and other manifestations. A 27-year-old man reported symptoms of aphasia with agraphia and alexia in a review after CO intoxication. The patient received outpatient speech therapy, as well as repeated sessions of hyperbaric oxygen for 15 days, interspersing speech therapy with hyperbaric oxygen therapy for two months. After this period of combined treatment the aphasic symptomatology remitted, and oral and written language was normal. The complete disappearance of aphasia with agraphia and alexia confirms the efficacy of the combined intervention. More data from large clinical studies are needed to assess the outcomes of hyperbaric oxygen treatment in patients with delayed neurological sequelae after CO intoxication, but this case suggests it may be a good therapeutic option in combination with specific speech therapy.

A predictive model for serious adverse events in adults with acute poisoning in prehospital and hospital care.

OBJECTIVE: The objective of this study was to design a risk model with variables determined before hospital arrival to predict the risk of serious adverse events in patients with acute poisoning. METHODS: A preliminary prospective, multicentre cohort study of adults with prehospital diagnosis of acute intoxication was conducted. The study was carried out in the Public Health System of the Community of Castilla-Leon (Spain), including seven advanced life support units and five hospitals, between April 1, 2018, and June 30, 2019. People aged >18 years with a main prehospital diagnosis of acute poisoning admitted to a referral hospital on advanced life support were included. The main outcome measure was prehospital and hospital serious adverse events in patients with acute poisoning. RESULTS: We included 221 patients, with a median age of 47 years (interquartile range: 33-61). The most frequent cause of poisoning was psychopharmaceuticals (111 cases, 49.8%): 38 (17.2%) patients had a serious adverse event, with a hospital mortality of 4.1% (nine cases) in the 30 days after the index event. The final model included age ≥65 years (odds ratio [OR]: 9.59, 95% confidence interval [CI]: 3.48-26.45; p < 0.001), oxygen saturation/fraction of inspired oxygen index ≤300 (OR: 15.03, 95% CI: 5.74-39.33; p < 0.001), and point-of-care lactate ≥4 mmol/L (OR: 7.68, 95% CI: 2.88-20.45; p < 0.001). The poisoning Early Warning Score was constructed from these three variables, and 1 point was assigned to each variable. The area under the curve of the score was 0.896 (95% CI: 0.82-0.96; p < 0.001). CONCLUSIONS: The poisoning Early Warning Score may help in decision-making and promote early identification of high-risk patients with acute poisoning in the prehospital context.

Association Between Bat Vitamin D Receptor 3' Haplotypes and Vitamin D Levels at Baseline and a Lower Response After Increased Vitamin D Supplementation and Exposure to Sunlight.

Objective: The aim of this study was to evaluate the relationship between vitamin D levels at baseline and after 12 weeks of supplementation/exposure to sunlight and VDR genotypes (BsmI, TaqI and ApaI) and haplotypes in a homogeneous population of postmenopausal women. Methods: We made a prospective study in which 151 women were randomized to two groups: One with 1000 mg of calcium and 800 IU vitamin D supplementation (102 women) and a placebo group with neither calcium or vitamin D supplementation (49 women). The follow-up was from May to September 2012.Vitamin D was determined by chemiluminescent immunoassay. Genotypes were determined using the Sequenomi Plexplatform and haplotypes using PHASE software. Results: Baseline (25 ± 10 ng/mlvs.23 ± 9 ng/ml, p > 0.05) and 12-week (32 ± 8 ng/mlvs.29 ± 10 ng/ml, p > 0.05) vitamin D levels were similar between the two groups. The genetic study was made in the total population. There were no differences in baseline and final levels of vitamin D in terms of genotypes and haplotypes, except for the Bat haplotype, whose baseline values were lower (25OHD: 21 ± 10 ng/mlvs. 21 ± 10 ng/ml, p = 0.038). The rate of nonresponders in this group was 15 % (p = 0.001), compared with 9 %, 2 % and 3 % in the other groups. Conclusions: The Bat haplotype was associated with lower baseline levels of vitamin D and a worse response to supplementation and, therefore, may be a risk factor for vitamin D deficiency.

Estrogen receptor genes polymorphisms determine serum lipid profile in healthy postmenopausal women treated with calcium, vitamin D, and genistein.

Cardiovascular risk increases in women after menopause. Unfavorable lipid-lipoprotein changes due to a lack of estrogens may have an important role in this context. Estrogen actions are mainly mediated by their binding to two estrogen receptors (ERs) whose signaling may be conditioned by different factors. Calcium, vitamin D, and genistein, among others, cause a beneficial effect on serum lipid profile by its modulation. Some genetic factors can also determine this signal. We determined the possible additive effect of genistein on calcium and vitamin D supplementation regarding serum lipid profile changes and whether ER polymorphisms may mediate in this effect. We performed a prospective, double blind study in which women were randomized in two groups: one group received calcium and vitamin D and the other group received calcium, vitamin D and genistein. Subsequently, we studied rs9340799, rs928554, and rs4986938 ER polymorphisms in both groups. Our results showed that being a carrier of the variant allele G of rs928554 polymorphism was associated with a greater decrease in triglyceride levels and that the homozygous AA genotype of rs9340799 polymorphism was associated with a greater decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels after calcium, vitamin D, and genistein supplementation. This is the first report showing an association between polymorphisms in ER genes and an improvement of the serum lipid profile after taking calcium, vitamin D, and genistein supplementation in postmenopausal women. It reinforces the hypothesis that genetic factors are crucial in ER signalling.

Polymorphisms of the farnesyl diphosphate synthase gene modulate bone changes in response to atorvastatin.

Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.

Clinical features and predictors of delayed neurological syndrome in carbon monoxide poisoning: the AMICO study. / Caracterización clínica y factores predictivos de desarrollo de síndrome neurológico tardío en la intoxicación por monóxido de carbono: estudio AMICO.

OBJECTIVES: To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. MATERIAL AND METHODS: Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. RESULTS: A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P .001). CONCLUSION: The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs.

OBJETIVO: Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. METODO: Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. RESULTADOS: Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p 0,001). CONCLUSIONES: Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Differences in clinical signs and severity of intoxication due to street drugs in adolescents and young adults treated in emergency departments. / Características diferenciales en las manifestaciones clínicas y la gravedad de las intoxicaciones por drogas de abuso en adolescentes atendidos en servicios de urgencias en comparación con adultos jóvenes.

OBJECTIVES: To determine whether symptoms and levels of severity of intoxication from street drugs differ between adolescents and young adults who come to hospital emergency departments for treatment. MATERIAL AND METHODS: We studied a consecutive cohort of adolescents (aged 12-17 years) and young adults (aged 18-30 years) who were treated in 11 hospital emergency departments belonging to the Drug Abuse Network of Spanish Hospital Emergency Departments (REDURHE). Sociodemographic and clinical characteristics and level of severity were recorded for comparison between between adolescents and young adults, adjusted for sex, alcohol co-ingestion, and type of drug used. An intoxication was recorded as severe if at least 1 of the following indicators was present: cardiac arrest, tracheal intubation, intensive care unit admission, and in-hospital death. RESULTS: We included a total of 2181 patients: 249 adolescents (11.4%) and 1932 young adults (88.6%). Alcohol coingestion and use of multiple drugs were less common in adolescents, who had significantly more events related to cannabis (in 81.1% vs 49.0% of young adults) and benzodiazepines (13.3% vs 5.5%). The adolescents had significantly fewer intoxications from the use of cocaine (10.8% vs 45.1%), amphetamines (17.3% vs 32.3%), ketamine (0.4% vs 6.0%) and gamma-hydroxybutyrate (0.4% vs 4.0%). A higher proportion of adolescents than young adults presented with diminished consciousness (23.0% vs 16.9%), but fewer manifested anxiety (15.9% vs 26.3%), palpitations (11.0% vs 19.5%), or chest pain (2.8% vs 9.2%). The pattern of associations was similar in the subgroup of intoxications due to cannabis. The adjusted model confirmed that the adolescents were more likely to have diminished consciousness, with an odds ratio (OR) of 1.851 (95% CI, 1.204-2.844) and less likely to have anxiety (OR, 0.529 (95% CI, 0.347-0.807). Intoxication was severe in 46 patients overall (2.1%); in adolescents and young adults the proportions were 0.8% and 2.3%, respectively (P = 0.129). In adolescents, the OR was 0.568 (95% CI, 0.131-2.468) for severity; for component indicators, the ORs were 0.494 (95% CI, 0.063-3.892) for intubation and 0.780 (95% CI, 0.175-3.475) for intensive care unit admission. No deaths occurred. CONCLUSION: Adolescents requiring emergency care for street drug intoxication had co-ingested alcohol or taken multiple drugs less often than young adults. Cannabis was the drug most often used by adolescents, who presented more often with diminished consciousness but less often with anxiety. We detected no differences related to event severity.

OBJETIVO: Investigar si existen diferencias en las drogas, sintomatología y gravedad entre adolescentes y jóvenes atendidos por intoxicación por drogas en servicios de urgencias hospitalarios (SUH). METODO: Entre los pacientes consecutivos atendidos por consumo de drogas en los 11 SUH de la REDURHE (Red de estudio de Drogas en Urgencias Hospitalarios en España), se seleccionaron los adolescentes (edad = 12-17 años) y los jóvenes (edad = 18-30 años). Se compararon las características sociodemográficas, clínicas y la gravedad (evento adverso combinado ­EAC­: parada cardiorrespiratoria, intubación endotraqueal, ingreso en cuidados intensivos o muerte intrahospitalaria) en adolescentes y jóvenes, ajustadas por sexo, coingesta de etanol y drogas involucradas. RESULTADOS: Se incluyeron 2.181 pacientes (adolescentes = 249, 11,4%; jóvenes = 1.932, 88,6%). En adolescentes, la coingesta de etanol y múltiples drogas fue menos frecuente. Hubo significativamente más asistencias por cannabis (81,1% vs 49,0%) y benzodiacepinas (13,3% vs 5,5%) y menos por cocaína (10,8% vs 45,1%), anfetamínicos (17,3% vs 32,3%), ketamina (0,4% vs 6,0%) y gamma-hidroxibutirato (0,4% vs 4,0%). Los adolescentes presentaron más disminución de consciencia (23,0% vs 16,9%) y menos ansiedad (15,9% vs 26,3%), palpitaciones (11,0% vs 19,5%) y dolor torácico (2,8% vs 9,2%). Estas asociaciones se mantuvieron al analizar el subgrupo de intoxicados por cannabis. En el modelo ajustado, los adolescentes presentan más disminución de consciencia con (OR = 1,851, IC 95%: 1,204-2,844) y menos ansiedad (OR = 0,529, IC 95%: 0,347-0,807). Se observó EAC en 46 pacientes (2,0%; 0,8% vs 2,3%, p = 0,129). La OR ajustada en adolescentes para EAC fue 0,568 (IC 95%: 0,131-2,468), y para intubación 0,494 (IC 95%: 0,063-3,892) y para ingreso en intensivos 0,780 (IC 95%: 0,175-3,475). No hubo fallecimientos. CONCLUSIONES: Los adolescentes intoxicados por drogas atendidos en SUH presentan con menor frecuencia coingesta de etanol o múltiples drogas. La droga más frecuentemente implicada es el cannabis, y presentan más disminución de consciencia y menos ansiedad. No detectamos diferencias en la gravedad entre adolescentes y jóvenes.

Long-term visual pathway alterations after elemental mercury poisoning: report of a series of 29 cases.

BACKGROUND: There are few clinical data on retinal involvement after acute exposure to high concentrations mercury and the available reports are based on a small number of patients suffering chronic exposure. The purpose of this paper is to report findings in workers acutely exposed to very high concentrations of mercury vapor with the aim of providing data on a possible direct retinal involvement. METHODS: Twenty-nine patients and 16 controls were evaluated in a comparative case series. Mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The correlations between variables also were studied. In addition, electrophysiological data from those patients with deeper VF defects (group 1) were compared with a normal control group. RESULTS: Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy. The VA was slightly affected in 48.27% (n = 14) of subjects. Loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n = 28) and 44.8% (n = 13), respectively. VF alterations were identified in 72.4% (n = 21) patients. No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP (p < 0.05). The reduced amplitude of the b wave at the ffERG, of the P50 at the PERG and of the P1 wave at the mfERG results (p < 0.05) suggested that the outer retina was involved. Significant negative correlations among blood mercury levels, VA, and ffERG were observed. CONCLUSIONS: In this case series, showed that acute exposure to mercury vapor had a hazardous effect on the visual system. Although neurologic and visual pathway involvement was clearly demonstrated, the differences found compared to control support the existence of a direct functional retinal damage and participation in impaired vision in mercury poisoning.

Ocular Surface Pathology in Patients Suffering from Mercury Intoxication.

PURPOSE: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication. DESIGN: Cross-sectional study. PARTICIPANTS: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects. METHODS: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM). RESULTS: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (-2.57 (-1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm2), nerve branching density (2 (2.50) n/mm2), and dendritic cell density (9.1 (8.84) n/mm2) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels. CONCLUSIONS: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

Arsenic, cadmium, and selenium exposures and bone mineral density-related endpoints: The HORTEGA study.

BACKGROUND AND OBJECTIVES: Experimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old. METHODS: In N = 1365 Hortega Study participants >20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure. RESULTS: The median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 µg/g creatinine, and 84.9 µg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < -1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 µg/L, which became increasingly positive above ~105 µg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of Se with the incidence of osteoporosis-related bone fractures, the positive association above ~105 µg/L was markedly stronger, compared to the cross-sectional analysis. CONCLUSIONS: Our results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Spanish Research Network on Drugs in Hospital Emergency Departments - the REDUrHE registry: general analysis and comparisons between weekend and weekday poisonings. / Red de Estudio de Drogas en Urgencias Hospitalarias en España (Registro REDUrHE): análisis general y comparación según asistencia en día laborable o festivo.

OBJECTIVES: To describe the sociodemographic characteristics, drug use patterns, and the severity of drug overdoses treated in hospital emergency departments according to the registry of the Spanish Research Network on Drugs in Hospital Emergency Departments (REDUrHE project), and to identify differences between patterns on weekdays and weekends/national holidays. MATERIAL AND METHODS: Eleven hospitals participated in the REDUrHE project, studying consecutive patients with symptoms of drug overdose over a 24-month period. The drugs implicated were extracted from clinical records or toxicology reports. An overdose was considered severe if management required intubation, cardiopulmonary resuscitation, or admission to the intensive care unit, or if in-hospital death occurred (composite event). Each of these variables was also analyzed by itself. RESULTS: A total of 4526 patients were studied (2218 [49%] on weekends/holidays; 2308 [51%] on workdays). The mean (SD) age was 33 (11) years, and 75.5% were men. The most commonly used drugs were cocaine (47.8%), paciencannabis (44.4%), amphetamine derivatives (25.5%), benzodiazepines (8.8%), and opioids (7.3%). Patients treated on weekends/holidays were younger (32.1 vs 33.1 years on weekdays, P = .006), and they were more often taken to the hospital in an ambulance (60.5% vs 57.3%, P = .035). Hospitals in large cities (Barcelona and Madrid) saw more patients on weekends/holidays (55.8%). Major tourist destinations (the Balearic and Canary Islands) saw fewer patients on weekends/holidays (44.7%, P .001). Alcohol was ingested along with a drug by 58.2%; this combination was more common on weekends/holidays (in 63.3% vs 52.9% on weekdays, P .001), and 39.4% used more than 1 drug. Use of more than 1 drug was less common on weekends (in 37.6% vs 41.2%, P = .013). Opioid emergencies were also less frequent on weekends (6.0% vs 8.6%, P = .001), when gamma-hydroxybutyrate (GHB) overdoses were more common (5.8% vs 3.6%, P .001). Severity indicators were present (the composite event) more often on weekends (in 3.6% vs 2.2%, P = .006). Likewise, weekends saw more intubations (in 2.3% vs 1.0%, P = .001) and intensive care unit admissions (2.4% vs 1.6%, P = .047). Twelve patients (0.3%) died; mortality was similar on weekends (0.2%) and weekdays (0.3%) (P = .826). After adjusting for age, sex, combined use of alcohol, and type of drug, the risk of the severe-event composite was greater on weekends (odds ratio, 1.569; 95% CI, 1.088-2.263). CONCLUSION: Weekend and holiday emergencies due to drug overdoses are more frequent in large city hospitals. Weekend emergencies share certain distinctive characteristics: patients are younger, alcohol more often is ingested with drugs but multiple-drug combinations are less common, and GHB is used more often while opioids are used less often. Severe poisonings occur more often on weekends and holidays.

OBJETIVO: Conocer las características sociodemográficas, el patrón de consumo y la gravedad de los pacientes atendidos en servicios de urgencias hospitalarios (SUH) españoles por intoxicación por drogas (Proyecto REDUrHE) e investigar si existen diferencias entre los días festivos y los días laborables. METODO: Once SUH integrantes del proyecto REDUrHE incluyeron durante 24 meses de forma consecutiva a los pacientes atendidos por sintomatología derivada del consumo de drogas ilegales. Estas se determinaron por la historia clínica o la determinación toxicológica. El indicador primario de gravedad fue el evento adverso combinado formado por intubación, parada cardiorrespiratoria, ingreso en cuidados intensivos o muerte intrahospitalaria y los indicadores secundarios cada uno de estos eventos adversos considerado individualmente. RESULTADOS: Se incluyeron 4.526 pacientes (festivo: 2.218, 49%; laborables: 2.308, 51%), con edad media de 33 años (DE 11) y 75,5% hombres. Las drogas más frecuentemente involucradas fueron cocaína (47,8%), cannabis (44,4%), derivados anfetamínicos (25,5%), benzodiacepinas (8,8%) y opiáceos (7,3%). Los pacientes atendidos en festivos eran más jóvenes (32,1 vs 33,1 años, p = 0,006) y más frecuentemente traídos al SUH en ambulancia (60,5% vs 57,3%, p = 0,035). Los SUH de grandes ciudades (Barcelona, Madrid) tuvieron la mayor afluencia en festivo (55,8%) y los de zonas de alto turismo lúdico (Baleares, Canarias) los de menor afluencia (44,7%; p 0,001). El 58,2% ingirió simultáneamente etanol (más en festivos, 63,3% vs 52,9%, p 0,001) y el 39,4% más de una droga (menos en festivos, 37,6% vs 41,2%, p = 0,013). En festivo, los opiáceos fueron menos frecuentes (6,0% vs 8,6%, p = 0,001) y el gamma- hidroxibutirato más (5,8% vs 3,6%, p 0,001). También en festivo, hubo más eventos combinados adversos (3,6% vs 2,2%; p = 0,006), más intubaciones (2,3% vs 1,0%, p = 0,001) y más ingresos en cuidados intensivos (2,4% vs 1,6%, p = 0,047). Fallecieron 12 pacientes (0,3%), sin diferencias entre grupos (0,2% vs 0,3%, p = 0,826). Al ajustar por edad, sexo, ingesta combinada de etanol y tipos de drogas implicadas, los pacientes atendidos en festivos tuvieron más riesgo de evento adverso combinado, con OR = 1,569 (IC 95% = 1,088-2,263). CONCLUSIONES: Las intoxicaciones por drogas atendidas en SUH en día festivo suceden con mayor frecuencia en grandes ciudades y presentan ciertas características distintivas (pacientes más jóvenes, más ingesta conjunta con etanol, menos combinación de drogas, más frecuente gamma-hidroxibutirato y menos frecuente piáceos). Durante los festivos, las intoxicaciones atendidas son de mayor gravedad.

Relationship between Insulin Resistance (HOMA-IR), Trabecular Bone Score (TBS), and Three-Dimensional Dual-Energy X-ray Absorptiometry (3D-DXA) in Non-Diabetic Postmenopausal Women.

BACKGROUND: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments. METHODS: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR. RESULTS: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c. CONCLUSIONS: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.

[Acute poisoning by chemical products: analysis of the first 15 years of the Spanish Toxic Surveillance System (SETv)]. / Intoxicaciones agudas por productos químicos: análisis de los primeros 15 años del Sistema Español de Toxicovigilancia (SETv).

OBJECTIVE: There are few epidemiological studies on acute poisonings from pesticides, industrials and household products in Spain. The objective of this work is to describe the epidemiological and clinical profile of acute poisonings by chemical products in our country, and analyze their annual evolution. METHODS: The Spanish Toxicovigilance System (SETv) is a prospective registry that includes 32 Emergency Departments and Intensive Care Units in Spain. An observational descriptive study of acute poisoning by chemical agents (excluding pharmacological products and illicit drugs) was carried out, within 1999-2014. Statistical analysis was performed using Chi-square or exact Fisher's tests. Non-parametric continuous variables were compared using the Mann-Whitney U test. P-value less than 0.05 were considered significant. RESULTS: The 10,548 cases studied had a mean age of 38.41 (±22.07) years, being significantly higher in women (p=0.0001). 67.7% of the poisonings occurred at home, and the most frequent routes of exposure were respiratory (48.3%), digestive (35.3%) and ocular (13.1%). The most frequent toxic groups were toxic gases (31%), caustics (25.6%) and irritant gases (12.1%). Of the patients that required treatment (76.2%), antidotes were used in 27.2%. 20.6% of the patients were admitted at Hospital, with a median stay of 32 (±151.94) days, with significant differences for pesticides and solvents (p=0.02). Sequelae were presented at discharge in 2.1% of patients. Mortality was 1.4% (146 patients) with a mean age of 62.08 years (±19.58) (p=0.0001). CONCLUSIONS: The reduction of chemical poisonings should be prevented in the domestic environment, taking into account the sources of exposure to carbon monoxide and the handling of household cleaning products, both caustic liquids and the generation of irritating gases when mixed.

OBJETIVO: Existen pocos estudios epidemiológicos, sobre todo de tipo multicéntrico, sobre las intoxicaciones agudas a causa de productos químicos agroindustriales y del hogar en España. El objetivo de este trabajo fue describir el perfil epidemiológico y clínico de estas intoxicaciones en nuestro país, y analizar su evolución temporal. METODOS: El Sistema Español de Toxicovigilancia (SETv) es un registro prospectivo que incluye a 32 Servicios de Urgencias y Unidades de Cuidados intensivos de España. Se realizó un estudio descriptivo observacional de las intoxicaciones agudas por agentes químicos (excluyendo drogas y fármacos) en sus primeros 15 años de funcionamiento (1999-2014). Las comparaciones de proporciones se realizaron mediante las pruebas de Chi-cuadrado o exacta de Fisher, y entre pares de grupos independientes con la prueba de Mann-Whitney. Se consideraron significativos los valores de probabilidad menores de 0,05. RESULTADOS: Los 10.548 casos estudiados presentaban una edad media de 38,41 (±22,07) años, siendo significativamente superior en las mujeres (p=0,0001). El 67,7% de las intoxicaciones ocurrieron en el hogar, y las vías de entrada más frecuentes fueron la respiratoria (48,3%), la digestiva (35,3%) y la ocular (13,1%). Los grupos tóxicos más frecuentes fueron los gases tóxicos (31%), los cáusticos (25,6%) y los gases irritantes (12,1%). Un 76,2% de los casos requirieron tratamiento (27,2% con antídotos). Ingresó en un centro hospitalario un 20,6% de las personas, con una estancia media de 32 (±151,94) días, con diferencias significativas para los plaguicidas y disolventes (p=0,02). Presentaron secuelas al alta un 2,1%. La mortalidad fue del 1,4% (146 pacientes), con una edad media de 62,08 años (±19,58; p=0,0001). CONCLUSIONES: En las intoxicaciones por productos químicos, las medidas preventivas deben centrarse fundamentalmente en el ámbito doméstico, controlando las fuentes de exposición al monóxido de carbono y la manipulación de los productos de limpieza, fundamentalmente los líquidos cáusticos y la generación de gases irritantes al mezclarlos.

Atorvastatin and BMD in coronary syndrome. Role of Lys656Asn polymorphism of leptin receptor gene.

OBJECTIVES: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome according to the Lys656Asn leptin receptor gene polymorphism. METHODS: Sixty-two patients with acute coronary syndrome were included. Patients were allocated to low and high doses of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk and were studied at hospital admission and at 12 months. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine and hip. Patients with a T-score<-2.5 were considered osteoporotic. The Lys656Asn leptin receptor gene polymorphism was determined by PCR. RESULTS: Forty-two patients were Lys/Lys homozygotic and 20 Lys/Asn heterozygotic. The prevalence of osteoporosis was 31% for the Lys/Lys genotype and 27% for the Lys/Asn genotype with no significant differences between groups. There was a significant increase in bone mineral density in the lumbar spine (1.117 +/- 0.24 versus 1.135 +/- 0.24, P = 0.008) in patients with the Lys/Lys genotype. CONCLUSION: Atorvastatin increases lumbar spine bone mineral density only in patients with the Lys/Lys genotype of the Lys656Asn polymorphism.

The association of urine metals and metal mixtures with cardiovascular incidence in an adult population from Spain: the Hortega Follow-Up Study.

BACKGROUND: The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting. RESULTS: In single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities. CONCLUSIONS: Urine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.

Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study.

INTRODUCTION: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. OBJECTIVES: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8­oxo­7,8­dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. RESULTS: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA. CONCLUSIONS: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation.