High Frequencies of Genetic Variants in Patients with Atypical Femoral Fractures.

This study explores the genetic factors associated with atypical femoral fractures (AFF), rare fractures associated with prolonged anti-resorptive therapy. AFF are fragility fractures that typically appear in the subtrochanteric or diaphyseal regions of the femur. While some cases resemble fractures in rare genetic bone disorders, the exact cause remains unclear. This study investigates 457 genes related to skeletal homeostasis in 13 AFF patients by exome sequencing, comparing the results with osteoporotic patients (n = 27) and Iberian samples from the 1000 Genomes Project (n = 107). Only one AFF case carried a pathogenic variant in the gene set, specifically in the ALPL gene. The study then examined variant accumulation in the gene set, revealing significantly more variants in AFF patients than in osteoporotic patients without AFF (p = 3.7 × 10-5), particularly in ACAN, AKAP13, ARHGEF3, P4HB, PITX2, and SUCO genes, all of them related to osteogenesis. This suggests that variant accumulation in bone-related genes may contribute to AFF risk. The polygenic nature of AFF implies that a complex interplay of genetic factors determines the susceptibility to AFF, with ACAN, SUCO, AKAP13, ARHGEF3, PITX2, and P4HB as potential genetic risk factors. Larger studies are needed to confirm the utility of gene set analysis in identifying patients at high risk of AFF during anti-resorptive therapy.

Influence of meteorological factors on the severity of COVID-19 in Spain: Observational ecological study.

Objectives: Evaluating whether meteorological and geographical variables could be associated with the severity of COVID-19 in Spain. Methods: An ecological study was performed to analyze the influence of meteorological and geographical factors in hospital admissions and deaths due to COVID-19 in the 52 provinces of Spain (24 coastal and 28 inland regions), during the first three pandemic waves. Medical and mortality data were collected from the Carlos III Health Institute (ISCIII) and meteorological variables were requested to the Spanish State Meteorological Agency (AEMET). Results: Regarding the diagnosed cases it is remarkable that the percentage of patients hospitalized for COVID-19 was lower in the coastal provinces than in the inland ones (8.7 ± 2.6% vs. 11.5 ± 2.6%; p = 9.9 × 10-5). Furthermore, coastal regions registered a lower percentage of mortality than inland regions (2.0 ± 0.6% vs. 3.1 ± 0.8%; p = 1.7 × 10-5). Mean air temperature was inversely correlated both with COVID-19 hospitalizations (Rho: -0.59; p = 3.0 × 10-6) and mortality (Rho: -0.70; p = 5.3 × 10-9). In those provinces with a mean air temperature <10 °C mortality by COVID-19 was twice that of those with >16 °C. Finally, we found an association between mortality and the location of the province (coastal/inland), altitude, patient age and the average air temperature; the latter was inversely and independently correlated with mortality (non standardised B coeff.: -0.24; IC 95%: -0.31 to -0.16; p = 2.38 × 10-8). Conclusions: The average air temperature was inversely associated with COVID-19 mortality in our country during the first three waves of the pandemic.

Objetivos: Evaluar si factores meteorológicos y geográficos pudieron relacionarse con la gravedad de la COVID-19 en España. Métodos: Estudio ecológico, a escala provincial, que analiza la influencia de factores meteorológicos y geográficos en la hospitalización y mortalidad por COVID-19 en las 52 provincias españolas (24 costeras y 28 del interior), durante las tres primeras olas. Los datos de hospitalizaciones y mortalidad se obtuvieron del Instituto de Salud Carlos III (ISCIII). Los datos epidemiológicos del Instituto Nacional Estadística (INE) y la Red Nacional de Vigilancia Epidemiológica (RENAVE). Las variables meteorológicas de la Agencia estatal de meteorología (AEMET). Resultados: El porcentaje de pacientes hospitalizados por COVID-19, del total de personas infectadas, fue inferior en las provincias costeras que en las del interior peninsular (8,7 ± 2,6% vs. 11,5 ± 2,6%; p = 9,9 × 10−5). De igual manera la costa registró menor porcentaje de mortalidad que el interior peninsular (2,0 ± 0,6% vs. 3,1 ± 0,8%; p = 1,7 × 10−5). La temperatura media correlacionó negativamente con la hospitalización (Rho: −0,59; p = 3,0 × 10−6) y la mortalidad por COVID-19 (Rho: −0,70; p = 5,3 × 10−9). Las provincias con una temperatura media <10 °C duplicaron la mortalidad por COVID respecto a las de >16 °C. La mortalidad se relacionó con la localización provincial (costa/interior), la altitud, la edad de la población y la temperatura media, siendo esta última la variable asociada de manera independiente (Coef. B no estandarizado: −0,24; IC 95%: −0,31 a −0,16; p = 2,38 × 10−8). Conclusiones: La mortalidad por COVID-19 durante las tres primeras olas de la pandemia en nuestro país se asoció inversamente con la temperatura media.

Influencia de los factores meteorológicos en la gravedad de la COVID-19 en España: estudio observacional ecológico / Influence of meteorological factors on the severity of COVID-19 in Spain: Observational ecological study

Objetivos: Evaluar si factores meteorológicos y geográficos pudieron relacionarse con la gravedad de la COVID-19 en España.MétodosEstudio ecológico, a escala provincial, que analiza la influencia de factores meteorológicos y geográficos en la hospitalización y en la mortalidad por COVID-19 en las 52 provincias españolas (24 costeras y 28 del interior) durante las tres primeras olas. Los datos de hospitalizaciones y de mortalidad se obtuvieron del Instituto de Salud CarlosIII (ISCIII); los datos epidemiológicos, del Instituto Nacional de Estadística (INE) y de la Red Nacional de Vigilancia Epidemiológica (RENAVE), y las variables meteorológicas, de la Agencia Estatal de Meteorología (AEMET).ResultadosEl porcentaje de pacientes hospitalizados por COVID-19, del total de personas infectadas, fue inferior en las provincias costeras que en las del interior peninsular (8,7±2,6% vs. 11,5±2,6%; p=9,9×10−5). De igual manera, la costa registró menor porcentaje de mortalidad que el interior peninsular (2,0±0,6% vs. 3,1±0,8%; p=1,7×10−5). La temperatura media correlacionó negativamente con la hospitalización (Rho: −0,59; p=3,0×10−6) y la mortalidad por COVID-19 (Rho: −0,70; p=5,3×10−9). Las provincias con una temperatura media <10°C duplicaron la mortalidad por COVID respecto a las de >16°C. La mortalidad se relacionó con la localización provincial (costa/interior), la altitud, la edad de la población y la temperatura media, siendo esta última la variable asociada de manera independiente (Coef.B no estandarizado: −0,24; IC95%: −0,31 a −0,16; p=2,38×10−8). (AU)

Objectives: Evaluating whether meteorological and geographical variables could be associated with the severity of COVID-19 in Spain.MethodsAn ecological study was performed to analyze the influence of meteorological and geographical factors in hospital admissions and deaths due to COVID-19 in the 52 provinces of Spain (24 coastal and 28 inland regions), during the first three pandemic waves. Medical and mortality data were collected from the CarlosIII Health Institute (ISCIII) and meteorological variables were requested to the Spanish State Meteorological Agency (AEMET).ResultsRegarding the diagnosed cases it is remarkable that the percentage of patients hospitalized for COVID-19 was lower in the coastal provinces than in the inland ones (8.7±2.6% vs. 11.5±2.6%; P=9.9×10−5). Furthermore, coastal regions registered a lower percentage of mortality than inland regions (2.0±0.6% vs. 3.1±0.8%; P=1.7×10−5). Mean air temperature was inversely correlated both with COVID-19 hospitalizations (Rho: −0.59; P=3.0×10−6) and mortality (Rho: −0.70; P=5.3×10−9). In those provinces with a mean air temperature <10°C mortality by COVID-19 was twice that of those with >16°C. Finally, we found an association between mortality and the location of the province (coastal/inland), altitude, patient age and the average air temperature; the latter was inversely and independently correlated with mortality (non-standardized β coeff.: −0.24; 95%CI: −0.31 to −0.16; P=2.38×10−8).ConclusionsThe average air temperature was inversely associated with COVID-19 mortality in our country during the first three waves of the pandemic. (AU)

Uncovering genetic causes of hypophosphatemia.

BACKGROUND: Chronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population. METHODS: By combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17-55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR). RESULTS: We identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X-linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities. CONCLUSION: Genetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype.

Utilidad de los enjuagues con povidona yodada y peróxido de hidrógeno en pacientes con COVID-19 / Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19

Introducción: La povidona yodada y el peróxido de hidrógeno podrían ser eficaces contra el SARS-CoV-2. Métodos: Estudio observacional de seguimiento prospectivo (EPA-AS) en 88 pacientes (43±17 años, 55% varones) con SARS-CoV-2 en muestras nasofaríngeas (RT-PCR). Treinta y uno recibieron enjuagues/gargarismos con povidona yodada cada 8h 2 días consecutivos, 17 con la misma pauta de peróxido de hidrógeno y 40 controles sin enjuagues. Se repitió PCR a los 3, 11 y 17 días. Resultados: Tras la intervención no hubo diferencias en la carga viral: povidona yodada (4,3±2,7 copias/ml), peróxido de hidrógeno (4,6±2,9 copias/ml), controles (4,4±3,0 copias/ml). El porcentaje de pacientes con una 2.ª PCR negativa fue 27% povidona yodada, 23% peróxido de hidrógeno y 32% controles; en la 3.ª PCR 62%, 54% y 58% respectivamente y en la 4.ª PCR, 81%, 75% y 81%. Conclusión: Nuestros resultados no apoyan la utilidad de los enjuagues de estos 2 antisépticos en pacientes con COVID-19.(AU)

Introduction: Povidone-iodine and hydrogen peroxide could be effective in against SARS-CoV-2. Methods: A “non-interventional trial” in 88 patients (43±17 yrs, 55% men) with SARS-CoV-2 in nasopharyngeal swabs (RT-PCR). 31 received mouth rinses/gargling with povidone-iodine (every 8h, two consecutive days), 17 with mouth rinses/gargling of hydrogen peroxide, and 40 controls. PCR were repeated at 3, 11 and 17 days. Results: After intervention the viral load (Log10copies/ml) remained similar in povidone-iodine (4.3±2.7copies/ml), hydrogen peroxide (4.6±2.9copies/ml; p=0.40) and controls (4.4±3.0copies/ml). The percentage of patients with a negative result in the second PCR was 27% in povidone-iodine group, 23% in hydrogen peroxide and 32% in controls; in the third PCR, 62%, 54% and 58% respectively; and in the fourth PCR, 81%, 75% and 81%. Conclusion: Our results do not support the clinical usefulness of mouth rinses/gargling with povidone-iodine or hydrogen peroxide in patients with COVID-19.(AU)

[Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19]. / Utilidad de los enjuagues con povidona yodada y peróxido de hidrógeno en pacientes con COVID-19.

Introduction: Povidone-iodine and hydrogen peroxide could be effective in against SARS-CoV-2. Methods: A "non-interventional trial" in 88 patients (43 ± 17 yrs, 55% men) with SARS-CoV-2 in nasopharyngeal swabs (RT-PCR). 31 received mouth rinses/gargling with povidone-iodine (every 8 h, two consecutive days), 17 with mouth rinses/gargling of hydrogen peroxide, and 40 controls. PCR were repeated at 3, 11 and 17 days. Results: After intervention the viral load (Log 10 copies/ml) remained similar in povidone-iodine (4.3 ± 2.7 copies/ml), hydrogen peroxide (4.6 ± 2.9 copies/ml; p = 0.40) and controls (4.4 ± 3.0 copies/ml). The percentage of patients with a negative result in the second PCR was 27% in povidone-iodine group, 23% in hydrogen peroxide and 32% in controls; in the third PCR, 62%, 54% and 58% respectively; and in the fourth PCR, 81%, 75% and 81%. Conclusion: Our results do not support the clinical usefulness of mouth rinses/gargling with povidone-iodine or hydrogen peroxide in patients with COVID-19.

[Influence of meteorological factors on the severity of COVID-19 in Spain: Observational ecological study]. / Influencia de los factores meteorológicos en la gravedad de la COVID-19 en España: estudio observacional ecológico.

OBJECTIVES: Evaluating whether meteorological and geographical variables could be associated with the severity of COVID-19 in Spain. METHODS: An ecological study was performed to analyze the influence of meteorological and geographical factors in hospital admissions and deaths due to COVID-19 in the 52 provinces of Spain (24 coastal and 28 inland regions), during the first three pandemic waves. Medical and mortality data were collected from the CarlosIII Health Institute (ISCIII) and meteorological variables were requested to the Spanish State Meteorological Agency (AEMET). RESULTS: Regarding the diagnosed cases it is remarkable that the percentage of patients hospitalized for COVID-19 was lower in the coastal provinces than in the inland ones (8.7±2.6% vs. 11.5±2.6%; P=9.9×10-5). Furthermore, coastal regions registered a lower percentage of mortality than inland regions (2.0±0.6% vs. 3.1±0.8%; P=1.7×10-5). Mean air temperature was inversely correlated both with COVID-19 hospitalizations (Rho: -0.59; P=3.0×10-6) and mortality (Rho: -0.70; P=5.3×10-9). In those provinces with a mean air temperature <10°C mortality by COVID-19 was twice that of those with >16°C. Finally, we found an association between mortality and the location of the province (coastal/inland), altitude, patient age and the average air temperature; the latter was inversely and independently correlated with mortality (non-standardized ß coeff.: -0.24; 95%CI: -0.31 to -0.16; P=2.38×10-8). CONCLUSIONS: The average air temperature was inversely associated with COVID-19 mortality in our country during the first three waves of the pandemic.

Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19.

INTRODUCTION: Povidone-iodine and hydrogen peroxide could be effective in against SARS-CoV-2. METHODS: A "non-interventional trial" in 88 patients (43±17 yrs., 55% men) with SARS-CoV-2 in nasopharyngeal swabs (RT-PCR). 31 received mouth rinses/gargling with povidone-iodine (every 8h, two consecutive days), 17 with mouth rinses/gargling of hydrogen peroxide, and 40 controls. Were repeated PCR in 3, 11 and 17 days. RESULTS: After intervention the viral load (Log10 copies/ml) remained similar in povidone-iodine (4.3±2.7 copies/ml), hydrogen peroxide (4.6±2.9 copies/ml; p=0.40) and controls (4.4±3.0 copies/ml). The percentage of patients with a negative result in the second PCR was 27% in povidone-iodine group, 23% in hydrogen peroxide and 32% in controls; in the third PCR, 62%, 54% y 58% respectively; and in the fourth PCR, 81%, 75% y 81%. CONCLUSION: Our results do not support the clinical usefulness of mouth rinses/gargling with povidone-iodine or hydrogen peroxide in patients with COVID-19.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

HIV screening and linkage to care in a health department in Valencia, Spain: Lessons learned from a healthcare quality improvement project.

Spain's rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08-0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63-33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.

Influence of weather factors on the incidence of COVID-19 in Spain.

Introduction: Several studies have analyzed the influence of meteorological and geographical factors on the incidence of COVID-19. Seasonality could be important in the transmission of SARS-CoV-2. This study aims to evaluate the geographical pattern of COVID-19 in Spain and its relationship with different meteorological variables. Methods: A provincial ecological study analyzing the influence of meteorological and geographical factors on the cumulative incidence of COVID-19 in the 52 (24 coastal and 28 inland) Spanish provinces during the first three waves was carried out. The cumulative incidence was calculated with data from the National Statistical Institute (INE) and the National Epidemiological Surveillance Network (RENAVE), while the meteorological variables were obtained from the Spanish Meteorological Agency (AEMET). Results: The total cumulative incidence, in all three waves, was lower in the coastal provinces than in the inland ones (566 ± 181 vs. 782 ± 154; P = 2.5 × 10-5). The cumulative incidence correlated negatively with mean air temperature (r = -0.49; P = 2.2 × 10-4) and rainfall (r = -0.33; P = .01), and positively with altitude (r = 0.56; P = 1.4 × 10-5). The Spanish provinces with an average temperature <10 °C had almost twice the cumulative incidence than the provinces with temperatures >16 °C. The mean air temperature and rainfall were associated with the cumulative incidence of COVID-19, regardless of other factors (Beta Coefficient of -0.62; P = 3.7 × 10-7 and -0.47; P = 4.2 × 10-5 respectively). Conclusions: Meteorological and geographical factors could influence the evolution of the pandemic in Spain. Knowledge regarding the seasonality of the virus would help to predict new waves of COVID-19 infections.

Introducción: Varios estudios han analizado la influencia de factores meteorológicos y geográficos en la incidencia de COVID-19. La estacionalidad podría tener importancia en la transmisión de SARS-CoV-2. Nuestro estudio evalúa el patrón geográfico de la COVID-19 en España y su relación con las distintas variables meteorológicas. Métodos: Estudio ecológico a escala provincial que analiza la influencia de factores meteorológicos y geográficos en la incidencia acumulada de COVID-19 en las 52 provincias españolas (24 costeras y 28 del interior) durante las tres primeras olas. La incidencia acumulada se calculó con los datos del Instituto Nacional Estadística (INE) y la Red Nacional de Vigilancia Epidemiológica (RENAVE), las variables meteorológicas se obtuvieron de la Agencia estatal de meteorología (AEMET). Resultados: La incidencia acumulada total, en los tres periodos, fue menor en las provincias costeras que en las del interior (566 ± 181 vs. 782 ± 154; P = 2,5 × 10−5). La incidencia acumulada correlacionó negativamente con la temperatura media (r = −0,49; P = 2,2 × 10−4) y las precipitaciones (r = −0,33; P = ,01), y positivamente con la altitud (r = 0,56; P = 1,4 × 10−5). Las provincias españolas con una temperatura media <10 °C tuvieron casi el doble de incidencia acumulada que las provincias con temperaturas >16 °C. La temperatura media y las precipitaciones fueron las variables asociadas con la incidencia acumulada provincial de COVID-19, con independencia de otros factores (Coeficiente Beta de −0,62; P = 3,7 × 10−7 y −0,47; P = 4,2 × 10−5 respectivamente). Conclusiones: Los factores meteorológicos y geográficos podrían influir en la evolución de la pandemia en España. El reconocimiento de la estacionalidad del COVID-19 ayudaría a predecir nuevas olas.

Influencia de los factores meteorológicos en la incidencia de COVID-19 en España / Influence of weather factors on the incidence of COVID-19 in Spain

Introducción: Varios estudios han analizado la influencia de factores meteorológicos y geográficos en la incidencia de COVID-19. La estacionalidad podría tener importancia en la transmisión de SARS-CoV-2. Nuestro estudio evalúa el patrón geográfico de la COVID-19 en España y su relación con las distintas variables meteorológicas.MétodosEstudio ecológico a escala provincial que analiza la influencia de factores meteorológicos y geográficos en la incidencia acumulada de COVID-19 en las 52 provincias españolas (24 costeras y 28 del interior) durante las tres primeras olas. La incidencia acumulada se calculó con los datos del Instituto Nacional de Estadística (INE) y la Red Nacional de Vigilancia Epidemiológica (RENAVE), las variables meteorológicas se obtuvieron de la Agencia Estatal de Meteorología (AEMET).ResultadosLa incidencia acumulada total, en los tres periodos, fue menor en las provincias costeras que en las del interior (566±181 vs. 782±154; p=2,5×10-5). La incidencia acumulada correlacionó negativamente con la temperatura media (r=-0,49; p=2,2×10-4) y las precipitaciones (r=-0,33; p=0,01), y positivamente con la altitud (r=0,56; p=1,4×10-5). Las provincias españolas con una temperatura media <10°C tuvieron casi el doble de incidencia acumulada que las provincias con temperaturas >16°C. La temperatura media y las precipitaciones fueron las variables asociadas con la incidencia acumulada provincial de COVID-19, con independencia de otros factores (Coeficiente Beta de -0,62; p=3,7×10-7 y -0,47; p=4,2x10-5, respectivamente).ConclusionesLos factores meteorológicos y geográficos podrían influir en la evolución de la pandemia en España. El reconocimiento de la estacionalidad del COVID-19 ayudaría a predecir nuevas olas. (AU)

Introduction: Several studies have analyzed the influence of meteorological and geographical factors on the incidence of COVID-19. Seasonality could be important in the transmission of SARS-CoV-2. This study aims to evaluate the geographical pattern of COVID-19 in Spain and its relationship with different meteorological variables.MethodsA provincial ecological study analyzing the influence of meteorological and geographical factors on the cumulative incidence of COVID-19 in the 52 (24 coastal and 28 inland) Spanish provinces during the first three waves was carried out. The cumulative incidence was calculated with data from the National Statistical Institute (INE) and the National Epidemiological Surveillance Network (RENAVE), while the meteorological variables were obtained from the Spanish Meteorological Agency (AEMET).ResultsThe total cumulative incidence, in all three waves, was lower in the coastal provinces than in the inland ones (566±181 vs. 782±154; p=2.5×10−5). The cumulative incidence correlated negatively with mean air temperature (r=−0.49; p=2.2×10−4) and rainfall (r=−0.33; p=0.01), and positively with altitude (r=0.56; p=1. 4×10−5). The Spanish provinces with an average temperature <10°C had almost twice the cumulative incidence than the provinces with temperatures >16°C. The mean air temperature and rainfall were associated with the cumulative incidence of COVID-19, regardless of other factors (Beta Coefficient of −0.62; p=3.7×10−7 and −0.47; p=4.2×10–5 respectively).ConclusionsMeteorological and geographical factors could influence the evolution of the pandemic in Spain. Knowledge regarding the seasonality of the virus would help to predict new waves of COVID-19 infections. (AU)

Pharmacogenetics of Osteoporosis: A Pathway Analysis of the Genetic Influence on the Effects of Antiresorptive Drugs.

Osteoporosis is a skeletal disorder defined by a decreased bone mineral density (BMD) and an increased susceptibility to fractures. Bisphosphonates and selective oestrogen receptor modulators (SERM) are among the most widely used drugs. They inhibit bone resorption by targeting the mevalonate and oestrogen pathways, respectively. The aim of this study was to determine if common variants of genes in those pathways influence drug responses. We studied 192 women treated with oral aminobisphosphonates and 51 with SERMs. Genotypes at 154 SNPs of the mevalonate pathway and 806 in the oestrogen pathway were analyzed. Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). These results suggest that genotyping genes in these pathways may help predict the response to antiresorptive drugs and hence make personalized therapeutic choices.

Procalcitonina es superior a recuento linfocitario, índice neutrófilo/linfocito y proteína C reactiva para la predicción de mortalidad a 30 días de pacientes con COVID-19 en el servicio de urgencias / Procalcitonin concentration in the emergency department predicts 30-day mortality in COVID-19 better than the lymphocyte count, the neutrophil-to- lymphocyte ratio, or the C-reactive protein level

Introducción. Existen múltiples variables demográficas y clínicas predictivas de mortalidad en pacientes con COVID-19. Sin embargo, hay menos información sobre el valor pronóstico de los biomarcadores inflamatorios. Métodos. Estudio de cohorte retrospectivo. Se incluyeron de forma consecutiva todos los pacientes con COVID-19, confirmado por laboratorio, atendidos en un servicio de urgencias hospitalario (SUH) y con valor basal de los siguientes biomarcadores: recuento linfocitario, índice neutrófilo/linfocito (INL), proteína C reactiva (PCR) y procalcitonina (PCT). La relación entre los biomarcadores y la mortalidad total a 30 días se analizó mediante una regresión de Cox y gráficos de dosis-respuesta. Resultados. Se incluyeron 896 pacientes, 151 (17%) fallecieron en los primeros 30 días. La mediana de edad fue de 63 años (51-78) y 494 (55%) eran hombres. El valor de INL, PCR y PCT fue mayor, mientras que el recuento linfocitario fue menor, en los pacientes que fallecieron respecto a los que sobrevivieron (p < 0,001). La PCT fue superior al recuento linfocitario, INL y PCR en la predicción de mortalidad a 30 días (ABC 0,79 [IC 95%: 0,75-0,83] vs 0,70 [IC 95%: 0,65-0,74], p < 0,001; 0,74 [IC 95%: 0,69-0,78], p = 0,03; y 0,72 [IC 95%: 0,68-0,76], p < 0,001). Los puntos de decisión de PCT propuestos, 0,06 ng/l para exclusión y 0,72 ng/l para inclusión de muerte a 30 días, podrían facilitar la toma de decisiones en urgencias. Hubo 357 pacientes (40%) con valores de PCT en estas categorías. El análisis multivariable mostró una mayor asociación con la mortalidad para PCT que en los otros biomarcadores estudiados. Conclusión. PCT es el biomarcador con mejor capacidad para predecir mortalidad a 30 días por cualquier causa en pacientes con COVID-19 valorados en un SUH.

Background. Although many demographic and clinical predictors of mortality have been studied in relation to COVID-19, little has been reported about the prognostic utility of inflammatory biomarkers. Methods. Retrospective cohort study. All patients with laboratory-confirmed COVID-19 treated in a hospital emergency department were included consecutively if baseline measurements of the following biomarkers were on record: lymphocyte counts, neutrophil-to-lymphocyte ratio NRL, and C-reactive protein (CRP) and procalcitonin (PCT) levels. We analyzed associations between the biomarkers and all-cause 30-day mortality using Cox regression models and dose–response curves. Results. We included 896 patients, 151 (17%) of whom died within 30 days. The median (interquartile range) age was 63 (51-78) years, and 494 (55%) were men. NLR, CRP and PCT levels at ED presentation were higher, while lymphocyte counts were lower, in patients who died compared to those who survived (P < .001). The areas under the receiver operating characteristic curves revealed the PCT concentration (0.79; 95% CI, 0.75-0.83) to be a better predictor of 30-day mortality than the lymphocyte count (0.70; 95% CI, 0.65-0.74; P < .001), the NLR (0.74; 95% CI, 0.69-0.78; P = .03), or the CRP level (0.72; 95% CI, 0.68-0.76; P < .001). The proposed PCT concentration decision points for use in emergency department case management were 0.06 ng/L (negative) and 0.72 ng/L (positive). These cutoffs helped classify risk in 357 patients (40%). Multivariable analysis demonstrated that the PCT concentration had the strongest association with mortality. Conclusion. PCT concentration in the emergency department predicts all-cause 30-day mortality in patients with COVID-19 better than other inflammatory biomarkers.

Risk factors in developing retinal vein occlusion in subject with obstructive sleep apnea.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) have a higher risk of developing vascular diseases. In this study, we evaluated the clinical profile of patients with OSA who develop Retinal Vein Occlusion (RVO) compared with a population of OSA patients without RVO. METHODS: We analysed patients with OSA diagnosed with RVO (21 cases; mean of age 61 (12) yrs. range 44-87 yrs. 67% men), belonging to a large cohort of people with long-term follow-up for RVO (up to 12 years). We compared them with 21 patients with OSA, without RVO, matched by age and gender, selected from the Sleep Unit Registry (control group). RESULTS: There were no differences in the prevalence of arterial hypertension (AHT) or Diabetes mellitus (DM), but the RVO patients presented a higher diastolic blood pressure compared to controls (87.6±12.6 mmHg vs. 77.9±10.1 mm Hg respectively). The polygraphic parameters were similar in both groups. The Apnoea-Hypopnoea Index (IHA) similar in both groups (30.4 ±20.9 RVO vs. 33.7 ± 22.1 controls). In addition, RVO patients had a less favourable lipid profile, with higher total cholesterol (218±52 mg/dL vs. 179±41 mg/dL), higher LDL cholesterol (139±47 mg/dL vs. 107±32 mg/dL) and higher atherogenic indices: LDL/HDL (2.78 ± 0.95 RVO vs. 2.03±0.67 controls) and total cholesterol / HDL (4.37± 1.08 vs. 3.45 ± 0.84). Among the cases, 81% had peripheral RVO (superior temporal branch in 20 out of 21 cases) and 19% had central RVO. 62% of the cases received intravitreal antiangiogenic therapy and dexamethasone implants and 33% received argon laser photocoagulation. CONCLUSIONS: Poor control of cardiovascular risk factors, particularly dyslipidaemias, in patients with OSA may lead to the development of this ocular complication.

Procalcitonin concentration in the emergency department predicts 30-day mortality in COVID-19 better than the lymphocyte count, the neutrophil-tolymphocyte ratio, or the C-reactive protein level. / Procalcitonina es superior a recuento linfocitario, índice neutrófilo/linfocito y proteína C reactiva para la predicción de mortalidad a 30 días de pacientes con COVID-19 en el servicio de urgencias.

OBJECTIVES: Although many demographic and clinical predictors of mortality have been studied in relation to COVID-19, little has been reported about the prognostic utility of inflammatory biomarkers. MATERIAL AND METHODS: Retrospective cohort study. All patients with laboratory-confirmed COVID-19 treated in a hospital emergency department were included consecutively if baseline measurements of the following biomarkers were on record: lymphocyte counts, neutrophil-to-lymphocyte ratio NRL, and C-reactive protein (CRP) and procalcitonin (PCT) levels. We analyzed associations between the biomarkers and all-cause 30-day mortality using Cox regression models and dose-response curves. RESULTS: We included 896 patients, 151 (17%) of whom died within 30 days. The median (interquartile range) age was 63 (51-78) years, and 494 (55%) were men. NLR, CRP and PCT levels at ED presentation were higher, while lymphocyte counts were lower, in patients who died compared to those who survived (P .001). The areas under the receiver operating characteristic curves revealed the PCT concentration (0.79; 95% CI, 0.75-0.83) to be a better predictor of 30-day mortality than the lymphocyte count (0.70; 95% CI, 0.65-0.74; P .001), the NLR (0.74; 95% CI, 0.69-0.78; P = .03), or the CRP level (0.72; 95% CI, 0.68-0.76; P .001). The proposed PCT concentration decision points for use in emergency department case management were 0.06 ng/L (negative) and 0.72 ng/L (positive). These cutoffs helped classify risk in 357 patients (40%). Multivariable analysis demonstrated that the PCT concentration had the strongest association with mortality. CONCLUSION: PCT concentration in the emergency department predicts all-cause 30-day mortality in patients with COVID-19 better than other inflammatory biomarkers.

OBJETIVO: Existen múltiples variables demográficas y clínicas predictivas de mortalidad en pacientes con COVID-19. Sin embargo, hay menos información sobre el valor pronóstico de los biomarcadores inflamatorios. METODO: Estudio de cohorte retrospectivo. Se incluyeron de forma consecutiva todos los pacientes con COVID-19, confirmado por laboratorio, atendidos en un servicio de urgencias hospitalario (SUH) y con valor basal de los siguientes biomarcadores: recuento linfocitario, índice neutrófilo/linfocito (INL), proteína C reactiva (PCR) y procalcitonina (PCT). La relación entre los biomarcadores y la mortalidad total a 30 días se analizó mediante una regresión de Cox y gráficos de dosis-respuesta. RESULTADOS: Se incluyeron 896 pacientes, 151 (17%) fallecieron en los primeros 30 días. La mediana de edad fue de 63 años (51-78) y 494 (55%) eran hombres. El valor de INL, PCR y PCT fue mayor, mientras que el recuento linfocitario fue menor, en los pacientes que fallecieron respecto a los que sobrevivieron (p 0,001). La PCT fue superior al recuento linfocitario, INL y PCR en la predicción de mortalidad a 30 días (ABC 0,79 [IC 95%: 0,75-0,83] vs 0,70 [IC 95%: 0,65-0,74], p 0,001; 0,74 [IC 95%: 0,69-0,78], p = 0,03; y 0,72 [IC 95%: 0,68-0,76], p 0,001). Los puntos de decisión de PCT propuestos, 0,06 ng/l para exclusión y 0,72 ng/l para inclusión de muerte a 30 días, podrían facilitar la toma de decisiones en urgencias. Hubo 357 pacientes (40%) con valores de PCT en estas categorías. El análisis multivariable mostró una mayor asociación con la mortalidad para PCT que en los otros biomarcadores estudiados. CONCLUSIONES: PCT es el biomarcador con mejor capacidad para predecir mortalidad a 30 días por cualquier causa en pacientes con COVID-19 valorados en un SUH.

Influence of weather factors on the incidence of COVID-19 in Spain. / Influencia de los factores meteorológicos en la incidencia de COVID-19 en España.

INTRODUCTION: Several studies have analyzed the influence of meteorological and geographical factors on the incidence of COVID-19. Seasonality could be important in the transmission of SARS-CoV-2. This study aims to evaluate the geographical pattern of COVID-19 in Spain and its relationship with different meteorological variables. METHODS: A provincial ecological study analyzing the influence of meteorological and geographical factors on the cumulative incidence of COVID-19 in the 52 (24 coastal and 28 inland) Spanish provinces during the first three waves was carried out. The cumulative incidence was calculated with data from the National Statistical Institute (INE) and the National Epidemiological Surveillance Network (RENAVE), while the meteorological variables were obtained from the Spanish Meteorological Agency (AEMET). RESULTS: The total cumulative incidence, in all three waves, was lower in the coastal provinces than in the inland ones (566±181 vs. 782±154; p=2.5×10-5). The cumulative incidence correlated negatively with mean air temperature (r=-0.49; p=2.2×10-4) and rainfall (r=-0.33; p=0.01), and positively with altitude (r=0.56; p=1. 4×10-5). The Spanish provinces with an average temperature <10°C had almost twice the cumulative incidence than the provinces with temperatures >16°C. The mean air temperature and rainfall were associated with the cumulative incidence of COVID-19, regardless of other factors (Beta Coefficient of -0.62; p=3.7×10-7 and -0.47; p=4.2×10-5 respectively). CONCLUSIONS: Meteorological and geographical factors could influence the evolution of the pandemic in Spain. Knowledge regarding the seasonality of the virus would help to predict new waves of COVID-19 infections.

Hyperbaric Oxygen Therapy Does Not Have a Negative Impact on Bone Signaling Pathways in Humans.

INTRODUCTION: Oxygen is emerging as an important factor in the local regulation of bone remodeling. Some preclinical data suggest that hyperoxia may have deleterious effects on bone cells. However, its clinical relevance is unclear. Hence, we studied the effect of hyperbaric oxygen therapy (HBOT) on serum biomarkers reflecting the status of the Wnt and receptor activator of NF-κB ligand (RANKL) pathways, two core pathways for bone homeostasis. MATERIALS AND METHODS: This was a prospective study of 20 patients undergoing HBOT (mean age 58 yrs., range 35-82 yrs.) because of complications of radiotherapy or chronic anal fissure. Patients were subjected to HBOT (100% oxygen; 2.4 atmospheres absolute for 90 min). The average number of HBOT sessions was 20 ± 5 (range 8-31). Serum hypoxia-inducible factor 1-α (HIF1-α), osteoprotegerin (OPG), RANKL, and the Wnt inhibitors sclerostin and dickkopf-1 (DKK1) were measured at baseline and after HBOT by using specific immunoassays. RESULTS: HIF-1α in eight patients with measurable serum levels increased from 0.084 (0.098) ng/mL at baseline to 0.146 (0.130) ng/mL after HBOT (p = 0.028). However, HBOT did not induce any significant changes in the serum levels of OPG, RANKL, sclerostin or DKK1. This was independent of the patients' diagnosis, either neoplasia or benign. CONCLUSION: Despite the potential concerns about hyperoxia, we found no evidence that HBOT has any detrimental effect on bone homeostasis.

Socio-Demographic Health Determinants Are Associated with Poor Prognosis in Spanish Patients Hospitalized with COVID-19.

INTRODUCTION: Social vulnerability is a known determinant of health in respiratory diseases. Our aim was to identify whether there are socio-demographic factors among COVID-19 patients hospitalized in Spain and their potential impact on health outcomes during the hospitalization. METHODS: A multicentric retrospective case series study based on administrative databases that included all COVID-19 cases admitted in 19 Spanish hospitals from 1 March to 15 April 2020. Socio-demographic data were collected. Outcomes were critical care admission and in-hospital mortality. RESULTS: We included 10,110 COVID-19 patients admitted to 18 Spanish hospitals (median age 68 (IQR 54-80) years old; 44.5% female; 14.8% were not born in Spain). Among these, 779 (7.7%) cases were admitted to critical care units and 1678 (16.6%) patients died during the hospitalization. Age, male gender, being immigrant, and low hospital saturation were independently associated with being admitted to an intensive care unit. Age, male gender, being immigrant, percentile of average per capita income, and hospital experience were independently associated with in-hospital mortality. CONCLUSIONS: Social determinants such as residence in low-income areas and being born in Latin American countries were associated with increased odds of being admitted to an intensive care unit and of in-hospital mortality. There was considerable variation in outcomes between different Spanish centers.

Influence of hyperbaric oxygen therapy on bone metabolism in patients with neoplasm.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is useful in the treatment of complications due to radiotherapy in patients with neoplasm. Its effects on bone metabolism are unclear. In our study, we analyzed the effects of HBOT on bone remodeling in oncological patients with radiotherapy. MATERIALS AND METHODS: Prospective clinical study in 23 patients with neoplasms undergoing treatment with HBOT due to complications of radiotherapy (hemorrhagic cystitis, proctitis or radionecrosis) and 25 patients with chronic anal fissure. The average number of HBOT sessions was 20 ± 5 (100% oxygen, 2.3 atmospheres and 90 min per day). Serum levels of aminoterminal propeptide of type I collagen (P1NP), C terminal telopeptide of type I collagen (CTX), alkaline phosphatase (AP), 25hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), were measured at 3 time points: T0 (before beginning HBOT), T1 (at the end of HBOT) and T2 (6 months after HBOT). RESULTS: At baseline, the patients with neoplasm have higher bone turnover than those with anal fissure. These differences were 41% in CTX (0.238 ± 0.202 ng/mL in neoplasm and 0.141 ± 0.116 ng/mL in fissure; p = 0.04), 30% for PTH (46 ± 36 pg/mL in neoplasm and 32 ± 17 pg/mL in fissure; p = 0.04) and 15% for alkaline phosphatase (80 ± 24 U/L in neoplasm and 68 ± 16 U/L in fissure; p = 0.04). In the group with neoplasm, the values of P1NP decreased 6% after HBOT (T0: 49 ± 31 ng/mL, T2: 46 ± 12 ng/mL; p = 0.03). Also, there were non-significant decreases in PTH (-34%) and CTX (-30%). CONCLUSIONS: Patients with neoplasm and complications with radiotherapy have an increase in bone remodeling that may be diminished after HBOT.