Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

Geochemical and mineralogical characterization of phosphogypsum and leaching tests for the prediction of the mobility of trace elements.

Phosphoric acid manufacturing generates large amounts of phosphogypsum (PG); a by-product generally disposed in the surface or evacuated in the seawater without any pretreatment. Phosphogypsum may host non-negligible amounts of valuable elements such as rare earth elements (REEs), which are critical elements on the global market. Surface disposal of PG may be a sustainable option to allow further processing in order to recover valuable elements. However, surface disposal exposes PG to atmospheric conditions (e.g., water, oxygen) which may increase their reactivity and accelerate the release rate of chemical species. This study aims to evaluate the trace element release rate from PG at atmospheric conditions. The studied PG samples were collected from a Moroccan phosphate treatment plant. The samples were characterized for their (i) chemical composition using inductively coupled plasma optical emission spectrometry (ICP-OES) for major elements and inductively coupled plasma mass spectrometry (ICP-MS) for trace elements; (ii) mineralogical composition by X-ray diffraction (XRD), scanning electron microscope equipped with energy-dispersive spectrometer (SEM-EDS), laser-induced breakdown spectroscopy (LIBS), and the mineral chemical composition was analyzed by electron probe microanalyzer (EPMA) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS); and (iii) chemical species release rate using leaching tests over 24 h at 25 and 60 °C. Chemically, the PG samples were mainly composed of Ca (23.03-23.35 wt.%), S (17.65-17.71 wt.%), and Si (0.75-0.82 wt.%), and non-negligible amounts of trace elements: REE (344-349 ppm), Cd (3.5-7.4 ppm), U (9.3-27.4 ppm). Mineralogically, the PGs are mainly formed by gypsum (94.2-95.9 wt.%) and quartz (1.67-1.76 wt.%). In terms of chemical species release, the PGs showed a higher reactivity at 60 °C compared to room temperature with a higher release rate at the beginning of the leaching tests. Quantitatively, the PG samples released 3.57-4.11 µg/L/day of REE, 3.18-17.29 µg/L/day of U, and 1.67-5.49 µg/L/day of Cd. Based on the leaching results, we concluded that the trace elements (e.g., U, Cd, REE) are incorporated in PG crystal lattice, which may explain their low concentrations in the leachates. Consequently, total digestion of PG matrix is required to solubilize REE.

Early redox homeostasis disruption contributes to the differential cytotoxicity of imiquimod on transformed and normal endothelial cells.

The off-label use of imiquimod (IQ) for hemangioma treatment has shown clinical benefits. We have previously reported a selective direct IQ-cytotoxic effect on transformed (H5V) vs. normal (1G11) endothelial cells (EC). In the present study, we investigated the mechanism underlying this selective cytotoxicity in terms of TLR7/8 receptor expression, NF-κB signalling and time-dependent modifications of oxidative stress parameters (ROS: reactive oxygen species, catalase and superoxide dismutase activities, GSH/GSSG and lipid peroxidation). TLR7/8 level was extremely low in both cell lines, and IQ did not upregulate TLR7/8 expression or activate NF-κB signalling. IQ significantly induced ROS in H5V after 2 h and strongly affected antioxidant defenses. After 12 h, enzyme activities were restored to baseline levels but a robust drop in GSH/GSSG persisted together with increased lipid peroxidation levels and a marked mitochondrial dysfunction. Although in normal IQ-treated EC some oxidative stress parameters were affected after 4 h, mitochondrial health and GSH/GSSG ratio remained notably unaffected after 12 h. Therefore, the early alterations (0-2 h) in transformed EC breached redox homeostasis as strongly as to enhance their susceptibility to IQ. This interesting facet of IQ as redox disruptor could broaden its therapeutic potential for other skin malignancies, alone or in adjuvant schemes.

Management of Perioperative Iron Deficiency Anemia.

Preoperative anemia affects 30-40% of patients undergoing major surgery and is an independent risk factor for perioperative blood transfusion, morbidity, and mortality. Absolute or functional iron deficiency is its leading cause. Nonanemic hematinic deficiencies are also prevalent and may hamper preoperative hemoglobin optimization and/or recovery from postoperative anemia. As modifiable risk factors, anemia and hematinic deficiencies should be detected and corrected prior to major surgical procedures. Postoperative anemia is even more common (up to 80-90%) due to surgery-associated blood loss, inflammation-induced blunted erythropoiesis, and/or preexisting anemia. Preoperative oral iron may have a role in mild-to-moderate anemia, provided there is sufficient time (6-8 weeks) and adequate tolerance of oral preparations. Postoperative oral iron is of little value and rife with gastrointestinal adverse events. Intravenous iron should preferentially be used in cases of moderate-to-severe iron deficiency anemia, concomitant use of erythropoiesis-stimulating agents, short time to surgery or nonelective procedures, and for postoperative anemia management. Minor infusion reactions to intravenous iron are rare, the incidence of severe anaphylactic reactions is extremely low, and there is no increase in infections with intravenous iron. Currently available intravenous iron formulations allowing administration of large single doses are preferred.

Short-term perioperative iron in major orthopedic surgery: state of the art.

In major orthopaedic surgery, it is recommended to detect and correct preoperative anaemia several weeks prior to surgery. However, in many cases, the procedure is urgent or the patient is evaluated shortly before the intervention. As iron deficiency is the leading cause of perioperative anaemia, an exhaustive review of the literature was performed to assess the efficacy and safety of short-term perioperative intravenous, with or without erythropoietin, or postoperative oral or intravenous supplementation in major orthopaedic surgery. Overall, 20 studies met the inclusion criteria. There were 13 randomized trials (moderate quality) and seven observational studies (low to very low quality). The primary outcomes were reduction in transfusion requirements, haemoglobin increase and medication side-effects during the study period. Data analysis showed that postoperative oral iron administration neither increased haemoglobin nor reduced transfusion requirements, and it was associated with significant gastrointestinal adverse effects (15%). In contrast, for some patient populations, perioperative or postoperative administration of intravenous iron, with or without recombinant erythropoietin, may reduce transfusion requirements and/or hasten the recovery from postoperative, with few clinically relevant adverse effects (<2%). However, discrepancies between randomized trials and observational studies on the possible beneficial effects of short-term perioperative intravenous iron administration were found for patients undergoing surgery for hip fracture repair. Further studies are needed to elucidate when the treatment should be started, which combination of drugs should be used, and which patient groups would be most benefit.

Sucrosomial® Iron: A New Generation Iron for Improving Oral Supplementation.

Iron deficiency (ID) is usually treated with oral iron salts, but up to 50% of patients complain of gastrointestinal side effects, leading to reduced treatment compliance. Intravenous (IV) iron formulations are increasingly safer, but there is still a risk of infusion and hypersensitivity reactions and the need for a venous access and infusion monitoring. Sucrosomial® iron (SI) is an innovative oral iron formulation in which ferric pyrophosphate is protected by a phospholipid bilayer plus a sucrester matrix (sucrosome), which is absorbed through para-cellular and trans-cellular routes (M cells). This confers SI unique structural, physicochemical and pharmacokinetic characteristics, together with high iron bioavailability and excellent gastrointestinal tolerance. The analysis of available evidence supports oral SI iron as a valid option for ID treatment, which is more efficacious and better tolerated than oral iron salts. SI has also demonstrated similar effectiveness, with lower risks, in patients usually receiving IV iron (e.g., chronic kidney disease, cancer, bariatric surgery). Thus, oral SI emerges as a most valuable first option for treating ID, even more for subjects with intolerance to or inefficacy of iron salts. Moreover, SI should be also considered as an alternative to IV iron for initial and/or maintenance treatment in different patient populations.

The safety of available treatment options for iron-deficiency anemia.

INTRODUCTION: Iron deficiency (ID), with or without anemia, is highly prevalent worldwide and has clinical consequences. The prevention and treatment of ID is a major public health goal. Accurate diagnosis, selection of the appropriate iron replacement therapy and addressing the underlying cause, remain as the main challenges in ID management. AREAS COVERED: This review aims to provide a narrative review of current available evidence on iron supplementation options regularly used to treat ID, including oral and intravenous (IV) iron formulations, with emphasis on safety issues. Analyzed safety concerns include gastrointestinal side effects (oral iron) and risks of hypotension, anaphylaxis, infection, hypophosphatemia, oxidative stress and mortality (IV iron). EXPERT OPINION: Low-to-moderate doses of oral iron supplementation remains as first line therapy for uncomplicated ID, but it has been scarcely discussed in the setting of inflammation. Confirmatory studies on the efficacy of newer oral iron formulations in this setting are needed. Compared with oral iron, short-term IV iron administration is more efficacious in ID correction, without significant safety concerns. However, long-term safety of IV iron maintenance therapy, head to head comparisons of IV iron preparations, pharmacological modulation of hepcidin and HIF, and extra-erythropoietic effects of iron are among the important areas of research.

Molecular mechanisms involved in the non-monotonic effect of bisphenol-a on ca2+ entry in mouse pancreatic ß-cells.

In regulatory toxicology, the dose-response relationship is a key element towards fulfilling safety assessments and satisfying regulatory authorities. Conventionally, the larger the dose, the greater the response, following the dogma "the dose makes the poison". Many endocrine disrupting chemicals, including bisphenol-A (BPA), induce non-monotonic dose response (NMDR) relationships, which are unconventional and have tremendous implications in risk assessment. Although several molecular mechanisms have been proposed to explain NMDR relationships, they are largely undemonstrated. Using mouse pancreatic ß-cells from wild-type and oestrogen receptor ERß-/- mice, we found that exposure to increasing doses of BPA affected Ca2+ entry in an NMDR manner. Low doses decreased plasma membrane Ca2+ currents after downregulation of Cav2.3 ion channel expression, in a process involving ERß. High doses decreased Ca2+ currents through an ERß-mediated mechanism and simultaneously increased Ca2+ currents via oestrogen receptor ERα. The outcome of both molecular mechanisms explains the NMDR relationship between BPA and Ca2+ entry in ß-cells.

Position paper on management of iron deficiency in adult cancer patients.

INTRODUCTION: Disorders of iron metabolism are commonly seen in onco-hematological clinical practice. Iron-deficiency anemia and cancer-associated anemia are usually treated with supportive therapies. Optimal management of these conditions are discussed in this perspective paper. Areas covered: A position paper discussing a number of hot topics on anemia in cancer patients is presented. The main areas covered by experts in the field are: definitions, prevalence and consequences of anemia and iron deficiency, incidence of anemia resulting from targeted therapies, importance of anemia diagnosis and monitoring, evaluation of iron status before and during treatment, role of transfusions and erythropoiesis-stimulating agents, management of iron deficiency with or without anemia, parenteral iron supplementation, role of new oral iron formulations, safety and cost issues regarding different iron compounds and administration routes. Expert commentary: Despite the availability of newer therapeutic options for its management, anemia still represents a major complication of treatment in cancer patients (surgery, chemotherapy, radiotherapy, targeted therapies), aggravating physical impairment, and negatively affecting general outcome. The view expressed by the panelists, attendees of the 4th Mediterranean Course on Iron Anemia, summarizes what they consider optimal clinical practice for screening, diagnosis, treatment and monitoring of iron deficiency and anemia in cancer patients.

Recommended vitamin D levels in the general population. / Recomendaciones de vitamina D para la población general.

OBJECTIVE: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes.

Recomendaciones de vitamina D para la población general / Recommended vitamin D levels in the general population

Objetivo: Proporcionar recomendaciones basadas en la evidencia sobre el manejo del déficit de vitaminaD en población general. Participantes: Miembros del Grupo de Trabajo de Osteoporosis y Metabolismo Mineral de la SEEN. Métodos: Se empleó el sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en Medline de la evidencia disponible para vitaminaD y el título de cada capítulo. Se revisaron artículos escritos en inglés con fecha de inclusión hasta 17 de marzo del 2016. Tras la formulación de las recomendaciones, estas se discutieron de manera conjunta en el grupo de trabajo. Conclusiones: Este documento resume los datos acerca del déficit de vitaminaD en lo que respecta a su prevalencia, etiología, indicaciones de cribado, niveles adecuados y efectos de la suplementación a nivel óseo y extraóseo (AU)

Objective: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. Participants: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. Methods: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. Conclusions: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes (AU)

'Patient blood management' en cirugía ortopédica / 'Patient blood management' in orthopaedic surgery

Los procedimientos de cirugía ortopédica y traumatológica (COT) pueden ocasionar pérdidas significativas de sangre y anemia postoperatoria aguda, que en muchos casos requiere transfusión de sangre alogénica (TSA). Las desventajas clínicas, económicas y logísticas de la TSA han promovido el desarrollo de programas multidisciplinares y multimodales, genéricamente conocidos como programas de Patient Blood Management (PBM), cuyo objetivo es el de reducir o eliminar la necesidad de TSA y mejorar el resultado clínico. Estos programas se apoyan en la aplicación de cuatro grupos de medidas perioperatorias: 1) uso de criterios restrictivos de transfusión; 2) estimulación de la eritropoyesis; 3) reducción del sangrado; y 4) transfusión de sangre autóloga. En este artículo, revisamos la eficacia, seguridad y recomendaciones de las estrategias aplicables en COT, así como los condicionantes para el desarrollo e implementación de los programas de PBM en esta especialidad (AU)

Orthopaedic and trauma surgical procedures (OTS) can lead to significant blood losses and acute postoperative anaemia, which in many cases requires allogeneic blood transfusions (ABT). The clinical, economic and logistical disadvantages of ABT have promoted the development of multidisciplinary and multimodal programs generically known as Patient Blood Management (PBM) programs, which have as their objective to reduce or eliminate the need for ABT and improve clinical outcomes. These programs are supported by the implementation of four groups of perioperative measures: (1) use of restrictive transfusion criteria; (2) stimulation of erythropoiesis; (3) reduction of bleeding; and (4) autologous blood transfusion. In this article, a review is presented of the effectiveness, safety and recommendations of applicable strategies in OTS, as well as the barriers and requirements to the development and implementation of PBM programs in this surgical specialty (AU)

Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN / Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working group on osteoporosis and mineral metabolism of the Spanish society of endocrinology

OBJETIVO: Actualizar las recomendaciones previas formuladas por el Grupo de trabajo de osteoporosis y metabolismo mineral de la Sociedad Española de Endocrinología y Nutrición (SEEN) para la evaluación y el tratamiento de la osteoporosis asociada a diferentes enfermedades endocrinas y alteraciones nutricionales. Participantes Miembros del Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN. MÉTODOS: Las recomendaciones se formularon de acuerdo al sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en PubMed de las nuevas acerca de cada enfermedad usando las siguientes palabras clave asociadas al nombre de cada proceso patológico: AND osteoporosis, fractures, bone mineral density, bone markers y treatment. Se revisaron artículos escritos en inglés con fechas de inclusión comprendidas entre el 18 de octubre de 2011 y el 30 de octubre de 2014. Tras la formulación de las recomendaciones estas se discutieron de forma conjunta por el Grupo de trabajo. CONCLUSIONES: Esta actualización resume los nuevos datos acerca de la evaluación y tratamiento de la osteoporosis en las enfermedades endocrinas y nutricionales que se asocian a baja masa ósea o a un aumento del riesgo de fractura

OBJECTIVE: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. PARTICIPANTS: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. Methods Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND 'osteoporosis', 'fractures', 'bone mineral density', and 'treatment'. Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. CONCLUSIONS: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions

[Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology]. / Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN.

OBJECTIVE: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. PARTICIPANTS: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. METHODS: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. CONCLUSIONS: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.

"Patient blood management" in orthopaedic surgery.

Orthopaedic and trauma surgical procedures (OTS) can lead to significant blood losses and acute postoperative anaemia, which in many cases requires allogeneic blood transfusions (ABT). The clinical, economic and logistical disadvantages of ABT have promoted the development of multidisciplinary and multimodal programs generically known as Patient Blood Management (PBM) programs, which have as their objective to reduce or eliminate the need for ABT and improve clinical outcomes. These programs are supported by the implementation of four groups of perioperative measures: (1) use of restrictive transfusion criteria; (2) stimulation of erythropoiesis; (3) reduction of bleeding; and (4) autologous blood transfusion. In this article, a review is presented of the effectiveness, safety and recommendations of applicable strategies in OTS, as well as the barriers and requirements to the development and implementation of PBM programs in this surgical specialty.

Guías de práctica clínica para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales / Clinical practice guidelines for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions

Objetivo Proporcionar unas recomendaciones prácticas para la evaluación y tratamiento de la osteoporosis asociada a diferentes enfermedades endocrinas y alteraciones nutricionales. Participantes Miembros del Grupo de Metabolismo Mineral de la Sociedad Española de Endocrinología y Nutrición, un metodólogo y un documentalista. Métodos Las recomendaciones se formularon de acuerdo al sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en Medline de la evidencia disponible para cada patología usando las siguientes palabras clave asociadas al nombre de cada patología: AND osteoporosis, fractures, bone mineral density, bone markers y treatment. Se revisaron artículos escritos en inglés con fecha de inclusión hasta 18 de octubre de 2011, y cada tema fue revisado por dos personas del Grupo. Un metodólogo resolvió las diferencias que surgieron durante el proceso de revisión de bibliografía y formulación de recomendaciones. Tras la formulación de las recomendaciones estas se discutieron en una reunión conjunta del Grupo de Trabajo. Conclusiones El documento establece unas recomendaciones prácticas basadas en la evidencia acerca de la evaluación y tratamiento de la osteoporosis en las enfermedades endocrinas y nutricionales que asocian baja masa ósea o aumento del riesgo de fractura. Para cada patología, se señala el riesgo de osteoporosis y fracturas asociado, se formulan recomendaciones en cuanto a la evaluación de masa ósea y se enumeran las opciones terapéuticas que han demostrado eficacia en aumentar la densidad mineral ósea y/o reducir el riesgo de fractura (AU)

Objective To provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions. Participants Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist. Methods Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts, related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group. Conclusions The document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed (AU)

[Clinical practice guidelines for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Bone Metabolism Working Group of the Spanish Society of Endocrinology]. / Guías de práctica clínica para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de Metabolismo Mineral de la Sociedad Espa˜nola deEndocrinología y Nutrición.

OBJECTIVE: To provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist. METHODS: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group. CONCLUSIONS: The document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed.

Intravenous iron therapy: how far have we come?

Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia (IDA) because of its effectiveness and low cost. But unfortunately in many iron deficient conditions, oral iron is a less than the ideal treatment mainly because of adverse events related to the gastrointestinal tract as well as the long course required to treat anemia and replenish body iron stores. The first iron product for intravenous use was high-molecular-weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to prescribe intravenous iron in the treatment of iron deficiency anemia for many years. In 1999 and 2001, two new intravenous iron preparations (ferric gluconate and iron sucrose) were introduced into the market as safer alternatives to iron dextran. Over the last five years, three new intravenous iron dextran-free preparations have been developed and have better safety profiles than the more traditional intravenous compounds, as none require test doses and all these products are promising in respect to a more rapid replacement of body iron stores (15-60 minutes/infusion) as they can be given at higher doses (from 500 mg to more than 1000 mg/infusion). The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, safety profile and toxicity of intravenous iron for the treatment of iron deficiency anemia.

Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).

The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).