Strontium ranelate effect on bone mineral density is modified by previous bisphosphonate treatment

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on bone mineral density (BMD) and boneturnover markers after 1 year of treatment. Additionally, theeffect of SrR in bisphosphonate-naïve patients (BP-naïve)compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included482 postmenopausal women treated with SrR (2 g/day) for 1year in ten Argentine centers; 41 patients were excludeddue to insufficient data, while 441 were included. Participants were divided according to previous bisphosphonatetreatment in two groups: BP-naïve (n = 87) and BP-prior (n = 350). Data are expressed as mean ± SEM. After 1 year oftreatment with SrR the bone formation markers total alkaline phosphatase and osteocalcin were increased (p < 0.0001),while the bone resorption marker s-CTX was decreased (p =0.0579). Also increases in BMD at the lumbar spine (LS,3.73%), femoral neck (FN, 2.00%) and total hip (TH, 1.54%) [p < 0.0001] were observed. These increments were significant(p < 0.0001) both among BP-naïve and BP-prior patients. Interestingly, the change in BMD after 1 year of SrR treatmentwas higher in BP-naïve patients: LS: BP-naïve = 4.58 ± 0.62%; BP-prior = 3.45 ± 0.28% (p = 0.078). FN: BP-naïve = 2.79 ±0.56%; BP-prior = 2.13 ± 0.29% (p = 0.161). TH: BP-naïve = 3.01± 0.55%; BP-prior = 1.22 ± 0.27% (p = 0.0006). SrR treatmentincreased BMD and bone formation markers and decreaseda bone resorption marker in the whole group, with betterresponse in BP-naïve patients.Fil: Brun, Lucas Ricardo Martín. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana M.. Hospital Italiano; ArgentinaFil: Vega, Eduardo. Instituto de la Mujer. Buenos Aires; ArgentinaFil: Salerni, Helena. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo ; ArgentinaFil: Maffei, Laura. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Premrou, Valeria. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Costanzo, Paulo R. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo ; ArgentinaFil: Sarli, Marcelo A. Instituto de Investigaciones Metabólicas Dr. Zanchetta; ArgentinaFil: Rey, Paula. Instituto de Investigaciones Metabólicas Dr. Zanchetta; ArgentinaFil: Larroudé, Maria S.. Hospital César Milstein; ArgentinaFil: Moggia, Maria S.. Centro Tiempo; ArgentinaFil: Brance, María Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; ArgentinaFil: Sánchez, Ariel. Centro de Endocrinología; ArgentinaFil: Grupo Argentino de Estudio del Ranelato de Estroncio. No especifica

Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified asresponders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responnders was higher with Dmab than with SrR.Fil: Sánchez, Ariel. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología SRL; ArgentinaFil: Brun, Lucas Ricardo Martín. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Salerni, Helena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Costanzo Caso, Pablo Alejandro. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Maffei, Ana Laura. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Pemrou, Valeria. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Sarli, Marcelo A.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Rey, Paula. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Larraoudé, María Silvia. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Hospital Milstein; ArgentinaFil: Brance, María Lorena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana María. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Servicio de Endocrinología del Hospital Italiano de Buenos Aires; ArgentinaFil: Gonzalez, Diana. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Bagur, Alicia Cristina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Vega, Eduardo. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Cesan; Argentina. Instituto de la Mujer; ArgentinaFil: Zanchetta, María B.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Farias, Vanina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Manzur, José L.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteoporosis; ArgentinaFil: Moggia, María S.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro Tiempo; ArgentinaFil: Ulla, María R.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteopatías Médicas; ArgentinaFil: Pavlove, María M.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Carlos Durand.; ArgentinaFil: Karlsbrum, Silvia. Hospital Durand; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Grupo Argentino de Estudio de la Osteoporosis. No especifíca

Densitometric Response in Postmenopausal Osteoporosis Treated with Strontium Ranelate or Denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR.Facultad de Ciencias Médica

Exploring Cosmic Origins with CORE: Cosmological Parameters

We forecast the main cosmological parameter constraints achievable with theCORE space mission which is dedicated to mapping the polarisation of the CosmicMicrowave Background (CMB). CORE was recently submitted in response to ESA'sfifth call for medium-sized mission proposals (M5). Here we report the resultsfrom our pre-submission study of the impact of various instrumental options, inparticular the telescope size and sensitivity level, and review the great,transformative potential of the mission as proposed. Specifically, we assessthe impact on a broad range of fundamental parameters of our Universe as afunction of the expected CMB characteristics, with other papers in the seriesfocusing on controlling astrophysical and instrumental residual systematics. Inthis paper, we assume that only a few central CORE frequency channels areusable for our purpose, all others being devoted to the cleaning ofastrophysical contaminants. On the theoretical side, we assume LCDM as ourgeneral framework and quantify the improvement provided by CORE over thecurrent constraints from the Planck 2015 release. We also study the jointsensitivity of CORE and of future Baryon Acoustic Oscillation and Large ScaleStructure experiments like DESI and Euclid. Specific constraints on the physicsof inflation are presented in another paper of the series. In addition to thesix parameters of the base LCDM, which describe the matter content of aspatially flat universe with adiabatic and scalar primordial fluctuations frominflation, we derive the precision achievable on parameters like thosedescribing curvature, neutrino physics, extra light relics, primordial heliumabundance, dark matter annihilation, recombination physics, variation offundamental constants, dark energy, modified gravity, reionization and cosmicbirefringence. (ABRIDGED

Repercussões do Sars-Cov-2 no âmbito da cirurgia geral e medicina de emergência: uma revisão

Na China, em dezembro de 2019, foram relatados os primeiros casos da patologia respiratória&nbsp; COVID-19, doença causado pelo SARS-CoV-2, um RNA vírus. A propagação foi veloz e global, de maneira que a Organização Mundial de Saúde definiu como pandemia em março de 2020. A doença tem manifestação clínica variada, com enfermos assintomáticos ou manifestando quadro crítico, apresentando alta transmissibilidade e letalidade considerável. Simultaneamente, indivíduos com indicação cirúrgica, de origem traumática ou não, tiveram seus atendimentos eletivos paralisados e houve queda nos índices de intervenções de cunho emergencista, tanto devido o medo do indivíduo procurar um serviço de saúde e ser contaminado pelo coronavírus, quanto por outros fatores. Essa revisão teve como objetivo averiguar como a pandemia acometeu serviços de cirurgia geral de emergência, bem como elucidar os preditores e fatores que ocasionaram mudanças no manejo e intervenções cirúrgicas durante o surto de SARS-CoV-2

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Variantes dispersivas para el operador de mutación en algoritmos genéticos con cromosmas binarios

Para algoritmos genéticos con cromosomas cuyos genes pueden tomar valores 0 o 1, analizamos la distribución del número de mutaciones por cromosoma con distintos operadores de mutación. Consideramos en primer lugar la operación clásica de recorrer las variables individuales binarias del cromosma y para cada una cambiar su valor independientemente con igual probabilidad μ, que resulta en una distribución binomial para el número de mutaciones por cromosoma. Luego definimos una familia de distribuciones de un parámetro que mantienen la media del operador binomial pero alteran la varianza con el fin de modificar el balance entre exploración y explotación en el espacio de búsqueda. Hallamos propiedades de dispersión de estos operadores y analizamos su desempeño en ensayos computacionales.Red de Universidades con Carreras en Informátic

Resumos em andamento - Saúde Coletiva

Resumos em andamento - Saúde Coletiv