Effect of Hydrogen Bonding and Chirality in Star-Shaped Molecules with Peripheral Triphenylamines: Liquid Crystal Semiconductors and Gels.

Organic semiconductors with well-defined architectures pose a suitable alternative to amorphous silicon-based inorganic semiconductors. Encouraged by the development of organic semiconductors based on columnar liquid crystals, herein, we report on a family of C3-symmetric star-shaped mesogens based on triphenylamine (TPA), a functional unit with strong electron donor character. Highly stable columnar phases with high hole mobility values were obtained out of this nonplanar functional unit, and this was achieved by using flexible amide spacers to join the TPA units to a tris(triazolyl)triazine (T) star-shaped core, allowing the formation of intermolecular hydrogen bonds. The presence of hydrogen bonds results in a stabilization of the columnar architectures either in bulk or in the presence of solvents by reinforcing π-stacking and van der Waals interactions, as deduced by Fourier-transform infrared (FTIR) and X-ray diffraction (XRD) studies. Furthermore, the introduction of a stereogenic center in the flexible spacer prompts the formation of chiral aggregates in the liquid crystal state and in the organogel formed in 1-octanol, as demonstrated by circular dichroism spectroscopy.

A Prospective, Observational Study of the Effect of a High-Calorie, High-Protein Oral Nutritional Supplement with HMB in an Old and Malnourished or at-Risk-of-Malnutrition Population with Hip Fractures: A FracNut Study.

BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Columnar liquid crystals based on antiaromatic expanded porphyrins.

Three naphthorosarins, antiaromatic expanded porphyrins bearing different meso substituents (NRos 1-3), designed to self-assemble into columnar liquid crystalline (LC) structures, were synthesized and characterized using polarized optical microscopy (POM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), as well as supporting computational calculations. The substituents were found to play a crucial role in modulating the LC behaviour.

In Vitro to In Vivo Scalars for Drug Clearance in Nonalcoholic Fatty Liver and Steatohepatitis.

In vitro-in vivo extrapolation (IVIVE) allows prediction of clinical outcomes across populations from in vitro data using specific scalars tailored to the biologic characteristics of each population. This study experimentally determined scalars for patients with varying degrees of nonalcoholic fatty liver disease (NAFLD), ranging from fatty liver to nonalcoholic steatohepatitis (NASH) and cirrhosis. Microsomal, S9, and cytosol fractions were extracted from 36 histologically normal and 66 NAFLD livers (27 nonalcoholic fatty liver [NAFL], 13 NASH, and 26 NASH with cirrhosis). Corrected microsomal protein per gram liver (MPPGL) progressively decreased with disease severity (26.8, 27.4, and 24.3 mg/g in NAFL, NASH, and NASH/cirrhosis, respectively, compared with 35.6 mg/g in normal livers; ANOVA, P < 0.001). Homogenate, S9, and cytosolic protein showed a consistent trend of decline in NASH/cirrhosis relative to normal control (post-hoc t test, P < 0.05). No differences across the groups were observed in homogenate, S9, cytosolic, and microsomal protein content in matched kidney samples. MPPGL-based scalars that combine protein content with liver size revealed that the reduction in MPPGL in NAFL and NASH was compensated by the reported increase in liver size (relative scalar ratios of 0.96 and 0.99, respectively), which was not the case with NASH/cirrhosis (ratio of 0.63), compared with healthy control. Physiologically based pharmacokinetics-informed global sensitivity analysis of the relative contribution of IVIVE scalars (hepatic CYP3A4 abundance, MPPGL, and liver size) to variability in exposure (area under the curve) to three CYP3A substrates (alprazolam, midazolam, and ibrutinib) revealed enzyme abundance as the most significant parameter, followed by MPPGL, whereas liver volume was the least impactful factor. SIGNIFICANCE STATEMENT: Nonalcoholic fatty liver disease-specific scalars necessary for extrapolation from in vitro systems to liver tissue are lacking. These are required in clearance prediction and dose selection in nonalcoholic fatty liver and steatohepatitis populations. Previously reported disease-driven changes have focused on cirrhosis, with no data on the initial stages of liver disease. The authors obtained experimental values for microsomal, cytosolic, and S9 fractions and assessed the relative impact of microsomal scalars on predicted exposure to substrate drugs using physiologically based pharmacokinetics.

Triphenylamine-Containing Benzoic Acids: Synthesis, Liquid Crystalline and Redox Properties.

The synthesis, characterization and liquid crystalline and electrochemical properties of novel triarylamines, in which the triphenylamine platform is non-symmetrically modified with a 4-(6-oxyhexyloxy)benzoic acid group, are reported. Compounds show columnar liquid crystalline behavior, as confirmed through the use of polarized optical microscopy, differential scanning calorimetry and X-ray diffraction. Electrochemical properties were measured using cyclic voltammperometry, obtaining low oxidation potentials and HOMO values that were optimum for consideration as organic semiconductors in hole transport layers. In addition, the photoredox activity of one of these derivatives in dichloromethane was studied under light irradiation. A photooxidation/assembly process under white light irradiation occurs without the assistance of hydrogen bonding amide functional groups.

Heparin-Coated Dendronized Hyperbranched Polymers for Antimalarial Targeted Delivery.

The rampant evolution of resistance in Plasmodium to all existing antimalarial drugs calls for the development of improved therapeutic compounds and of adequate targeted delivery strategies for them. Loading antimalarials in nanocarriers specifically targeted to the parasite will contribute to the administration of lower overall doses, with reduced side effects for the patient, and of higher local amounts to parasitized cells for an increased lethality toward the pathogen. Here, we report the development of dendronized hyperbranched polymers (DHPs), with capacity for antimalarial loading, that are coated with heparin for their specific targeting to red blood cells parasitized by Plasmodium falciparum. The resulting DHP-heparin complexes exhibit the intrinsic antimalarial activity of heparin, with an IC50 of ca. 400 nM, added to its specific targeting to P. falciparum-infected (vs noninfected) erythrocytes. DHP-heparin nanocarriers represent a potentially interesting contribution to the limited family of structures described so far for the loading and targeted delivery of current and future antimalarial compounds.

Dendron-functionalised hyperbranched bis-MPA polyesters as efficient non-viral vectors for gene therapy in different cell lines.

Gene therapy has become a relevant tool in the biomedical field to treat or even prevent some diseases. The effective delivery of genetic material into the cell remains a crucial step to succeed in this purpose. In the search for efficient non-viral vectors, a series of amino-terminated dendronized hyperbranched polymers (DHPs) of different generations based either on bis-MPA or bis-GMPA have been designed. All of them have demonstrated an accurate ability to complex two types of genetic materials, a plasmid DNA and a siGFP, yielding dendriplexes. Moreover, some of them have proved to be able to deliver the genetic material inside the cells, resulting in the effective accomplishment of the desired genetic modification and improving the activity of some commercial transfection reagents. Different cell lines, including cancer and mesenchymal stem cells, have been studied here to evaluate the ability of DHPs as vectors for transfection. Treatments based on mesenchymal stem cells are gaining importance due to their pluripotency. Thus, it is of special relevance to introduce a genetic modification into a mesenchymal cell line as it allows it to act over a wide spectrum of tissues after inducing cellular differentiation.

Improving hip fracture care in Spain: evolution of quality indicators in the Spanish National Hip Fracture Registry.

This study was carried out to analyze the evolution of the quality indicators in the Spanish National Hip Fracture Registry, after disseminating a series of recommendations based on available clinical practice guidelines to the participating hospitals. Six of the seven proposed quality indicators showed a significant improvement. PURPOSE: The Spanish National Hip Fracture Registry (RNFC) arises from the need to know the process and improve the quality of care. Our goal was to analyze the changes in the RNFC's quality indicators after an intervention based on disseminating specific recommendations among the participating hospitals, following available clinical practice guidelines. METHODS: Study comparing before and after performing an intervention in hospitals participating in the RNFC. Data from the hospitals that registered cases in 2017, and that kept registering cases in 2019. Seven quality indicators were chosen, and a standard to be achieved for each indicator was proposed. The intervention consisted in the dissemination of 25 recommendations with practical measures to improve each quality indicator, based on available clinical practice guidelines, by drafting and publishing a scientific paper and sending it via email and printed cards. Fulfilment of each quality indicator was measured after carrying out the intervention. RESULTS: Forty-three hospitals registered 2674 cases between January and May, 2017, and 8037 during 2019. The quality indicators chosen and the degree of compliance were (all with p<0.05): (1) surgery ≤48 h increased from 38.9 to 45.8%; (2) patients mobilised on the first postoperative day increased from 58.9 to 70.3%; (3) patients with anti-osteoporotic medication at discharge increased from 34.5 to 49.8%; (4) patients with calcium supplements at discharge increased from 48.7 to 62.8%; (5) patients with vitamin D supplements at discharge increased from 71.5 to 84.7%; (6) patients developing a grade >2 pressure ulcer during admission decreased from 6.5 to 5.0%; (7) patients able to move on their own at 1 month fell from 58.8 to 56.4%. More than 48% of hospitals improved the proposed indicators. CONCLUSION: Establishing quality indicators and standards and intervening through the dissemination of specific recommendations to improve these indicators achieved an improvement in hospital performance results on a national level.

Fluorescence Liquid Biopsy for Cancer Detection Is Improved by Using Cationic Dendronized Hyperbranched Polymer.

(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FSscore), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.

Combination Chemotherapy with Cisplatin and Chloroquine: Effect of Encapsulation in Micelles Formed by Self-Assembling Hybrid Dendritic-Linear-Dendritic Block Copolymers.

Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic® F127 hybrid dendritic-linear-dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2'-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2'-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously.

Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays.

The use of nanocarriers has been revealed as a valid strategy to facilitate drug bioavailability, and this allows for expanding the drug libraries for the treatment of certain diseases such as viral diseases. In the case of Hepatitis C, the compounds iopanoic acid and 3,3',5-triiodothyroacetic acid (or tiratricol) were identified in a primary screening as bioactive allosteric inhibitors of viral NS3 protease, but they did not exhibit accurate activity inhibiting viral replication in cell-based assays. In this work, dendritic nanocarriers are proposed due to their unique properties as drug delivery systems to rescue the bioactivity of these two drugs. Specifically, four different amphiphilic Janus dendrimers synthesized by combining 2,2'-bis(hydroxymethyl)propionic acid (bis-MPA) and 2,2'-bis(glyciloxy)propionic acid (bis-GMPA) functionalized with either hydrophilic or lipophilic moieties at their periphery were used to entrap iopanoic acid and tiratricol. Interestingly, differences were found in the loading efficiencies depending on the dendrimer design, which also led to morphological changes of the resulting dendrimer aggregates. The most remarkable results consist of the increased water solubility of the bioactive compounds within the dendrimers and the improved antiviral activity of some of the dendrimer/drug aggregates, considerably improving antiviral activity in comparison to the free drugs. Moreover, imaging studies have been developed in order to elucidate the mechanism of cellular internalization.

Promising nanomaterials in the fight against malaria.

For more than one hundred years, several treatments against malaria have been proposed but they have systematically failed, mainly due to the occurrence of drug resistance in part resulting from the exposure of the parasite to low drug doses. Several factors are behind this problem, including (i) the formidable barrier imposed by the Plasmodium life cycle with intracellular localization of parasites in hepatocytes and red blood cells, (ii) the adverse fluidic conditions encountered in the blood circulation that affect the interaction of molecular components with target cells, and (iii) the unfavorable physicochemical characteristics of most antimalarial drugs, which have an amphiphilic character and can be widely distributed into body tissues after administration and rapidly metabolized in the liver. To surpass these drawbacks, rather than focusing all efforts on discovering new drugs whose efficacy is quickly decreased by the parasite's evolution of resistance, the development of effective drug delivery carriers is a promising strategy. Nanomaterials have been investigated for their capacity to effectively deliver antimalarial drugs at local doses sufficiently high to kill the parasites and avoid drug resistance evolution, while maintaining a low overall dose to prevent undesirable toxic side effects. In recent years, several nanostructured systems such as liposomes, polymeric nanoparticles or dendrimers have been shown to be capable of improving the efficacy of antimalarial therapies. In this respect, nanomaterials are a promising drug delivery vehicle and can be used in therapeutic strategies designed to fight the parasite both in humans and in the mosquito vector of the disease. The chemical analyses of these nanomaterials are essential for the proposal and development of effective anti-malaria therapies. This review is intended to analyze the application of nanomaterials to improve the drug efficacy on different stages of the malaria parasites in both the human and mosquito hosts.

Repurposing Heparin as Antimalarial: Evaluation of Multiple Modifications Toward In Vivo Application.

Heparin is a promising antimalarial drug due to its activity in inhibiting Plasmodium invasion of red blood cells and to the lack of resistance evolution by the parasite against it, but its potent anticoagulant activity is preventing the advance of heparin along the clinical pipeline. We have determined, in in vitro Plasmodium falciparum cultures, the antimalarial activity of heparin-derived structures of different origins and sizes, to obtain formulations having a good balance of in vitro safety (neither cytotoxic nor hemolytic), low anticoagulant activity (≤23 IU/mL according to activated partial thromboplastin time assays), and not too low antimalarial activity (IC50 at least around 100 µg/mL). This led to the selection of five chemically modified heparins according to the parameters explored, i.e., chain length, sulfation degree and position, and glycol-split, and whose in vivo toxicity indicated their safety for mice up to an intravenous dose of 320 mg/kg. The in vivo antimalarial activity of the selected formulations was poor as a consequence of their short blood half-life. The covalent crosslinking of heparin onto the surface of polyethylene glycol-containing liposomes did not affect its antimalarial activity in vitro and provided higher initial plasma concentrations, although it did not increase mean circulation time. Finding a suitable nanocarrier to impart long blood residence times to the modified heparins described here will be the next step toward new heparin-based antimalarial strategies.

On the Structure and Chiral Aggregation of Liquid Crystalline Star-Shaped Triazines H-Bonded to Benzoic Acids.

The ability of a star-shaped tris(triazolyl)triazine derivative to hierarchically build supramolecular chiral columnar organizations through the formation of H-bonded complexes with benzoic acids was studied from a theoretical and experimental point of view. The combined study has been done at three different levels including the study of the structure of the triazine core, the association with benzoic acids in stoichiometry 1:3, and the assembly of 1:3 complexes in helical aggregates. Although the star-shaped triazine core crystallizes in a non-C3 conformation, the C3 -symmetric conformation is theoretically predicted to be more stable and gives rise to a favorable C3 supramolecular 1:3 complex upon the interaction with three benzoic acids in their voids. In addition, calculations at different levels (DFT, PM7, and MM3) for the 1:3 host-guest complex predict the formation of large stable columnar helical aggregates stabilized by the compact packing of the interstitial acids by π-π and CH⋅⋅⋅π interactions. The acids restrict the movement of the the star-shaped triazine cores along the stacking axis causing a template effect in the self-assembly of the complex. Theoretical predictions correlate with experimental results, since the interaction with achiral or chiral 3,4,5-(4-alkoxybenzyloxy)benzoic acids gives rise to supramolecular complexes that organize in bulk hexagonal columnar mesophases stable at room temperature with intracolumnar order. The existence of supramolecular chirality in the mesophase was determined for complexes formed by acids derived from (S)-2-octanol. Chiral aggregation was also evidenced for complexes formed in dodecane.

[Spanish National Hip Fracture Registry (RNFC): First-year results and comparison with other registries and prospective multi-centric studies from Spain]. / Registro Nacional de Fracturas de Cadera (RNFC): resultados del primer año y comparación con otros registros y estudios multicéntricos españoles.

OBJECTIVE: The Spanish National Hip Fracture Registry (Registro Nacional de Fracturas de Cadera or RNFC) is a Spanish, prospective, multi- centric registry, commenced in 2017. The goal of this paper is to present the data from the first annual report and to compare them with autonomic registries and recent prospective multi-centric studies performed in Spain. METHODS: We included persons 75 years or older treated for fragility hip fractures in any of the centers participating in the RNFC between January and October 2017. The descriptive statistics of each variable used the mean (and standard deviation) or the median (and interquartile ranges) for the ordinal variables and the percentage for the categoric variables. A descriptive analysis of the casemix was performed and compared with available data from the aforementioned studies. RESULTS: The RNFC included 7.208 patients from 54 hospitals, with a mean age of 86.7 (SD 5.6) years; 75.4% were women, and 36.4% showed cognitive decline. Mean surgical delay was 75.7 (SD 63.6) hours, and length of stay averaged 10.9 (SD 6.7) days. Of the patients who lived at home (75.4%), less than half (37.0%) returned home at discharge. One-month mortality was 7.1%. Comparison with other studies showed important differences, especially regarding patients newly sent to nursing homes (7.7-29.4%) and with antiosteoporotic treatment at discharge (14.5-36.7%). CONCLUSIONS: The RNFC is the largest prospective database to date that offers data regarding the characteristics of patients hospitalized for hip fractures in Spain. Comparison with recent studies showed some important differences.

OBJETIVO: El Registro Nacional de Fracturas de Cadera (RNFC) es un registro español multicéntrico, prospectivo y continuo, que comenzó en 2017. El objetivo de este artículo fue presentar los datos del primer informe anual y compararlos con los registros autonómicos y los estudios multicéntricos realizados recientemente en España. METODOS: Se incluyeron las personas de 75 años o más atendidas con el diagnóstico de fractura de cadera por fragilidad en alguno de los hospitales participantes en el RNFC, entre enero y octubre de 2017. En el análisis estadístico se utilizó la media y desviación estándar o mediana y rangos intercuartílicos para las variables numéricas y los porcentajes para las variables categóricas. Se realizó un análisis descriptivo global de la casuística y se comparó con los datos disponibles de los estudios previos mencionados. RESULTADOS: Se registraron 7.208 personas de 54 hospitales, con una edad media de 86,7 años (DE 5,6). El 75,4% fueron mujeres y el 36,4% presentaron deterioro cognitivo previo. La demora quirúrgica media fue de 75,7 horas (DE 63,6) y la estancia media fue de 10,9 días (DE 6,7). De las personas que vivían en un domicilio antes de la fractura (75,4%), menos de la mitad (37,0%) volvieron a él tras el alta hospitalaria. Al mes, había fallecido el 7,1%. La comparación con los otros estudios mostró algunas diferencias importantes, sobre todo en la ubicación previa, en el porcentaje de pacientes institucionalizados de novo (7,7-29,4%) y en el porcentaje con tratamiento antiosteoporótico al alta (14,5-36,7%). CONCLUSIONES: El RNFC es la mayor base de datos prospectiva que aporta datos sobre el perfil de los pacientes hospitalizados por fractura de cadera en España. La comparación con otros estudios recientes muestra algunas diferencias importantes.

Assessing Toxicokinetic Uncertainty and Variability in Risk Prioritization.

High(er) throughput toxicokinetics (HTTK) encompasses in vitro measures of key determinants of chemical toxicokinetics and reverse dosimetry approaches for in vitro-in vivo extrapolation (IVIVE). With HTTK, the bioactivity identified by any in vitro assay can be converted to human equivalent doses and compared with chemical intake estimates. Biological variability in HTTK has been previously considered, but the relative impact of measurement uncertainty has not. Bayesian methods were developed to provide chemical-specific uncertainty estimates for 2 in vitro toxicokinetic parameters: unbound fraction in plasma (fup) and intrinsic hepatic clearance (Clint). New experimental measurements of fup and Clint are reported for 418 and 467 chemicals, respectively. These data raise the HTTK chemical coverage of the ToxCast Phase I and II libraries to 57%. Although the standard protocol for Clint was followed, a revised protocol for fup measured unbound chemical at 10%, 30%, and 100% of physiologic plasma protein concentrations, allowing estimation of protein binding affinity. This protocol reduced the occurrence of chemicals with fup too low to measure from 44% to 9.1%. Uncertainty in fup was also reduced, with the median coefficient of variation dropping from 0.4 to 0.1. Monte Carlo simulation was used to propagate both measurement uncertainty and biological variability into IVIVE. The uncertainty propagation techniques used here also allow incorporation of other sources of uncertainty such as in silico predictors of HTTK parameters. These methods have the potential to inform risk-based prioritization based on the relationship between in vitro bioactivities and exposures.

Results of an anaemia treatment protocol complementary to blood transfusion in elderly patients with hip fracture.

BACKGROUND: Anaemia is a very common condition in elderly patients with hip fracture. The side effects of blood transfusions are well known, and further research on potential alternative therapies is needed. OBJECTIVES AND DESIGN: A non-controlled descriptive study, conducted on 138 patients admitted for hip fracture, aimed at analysing the effects of an anaemia treatment protocol adjunctive to transfusion, based on the use of supra-physiological doses of intravenous iron and erythropoietin (IS/EPOS). The variables collected were, medical history, physical and cognitive status prior to fracture, as well as the need of blood products, medical complications during admission and their functional outcome at three and six months after the fracture were evaluated. Transfusion rates were compared with a historical control group when the only treatment for acute anaemia was transfusion (2011). RESULTS: Almost half (63, 48%) of the patients received blood transfusion, with (91,70%) IS/EPOD. Intravenous iron did not reduce the percentage of transfused patients (56% vs. 44%), but it did reduce the number of blood units required (0.7 units less in IS/EPO group). Patients who required transfusion had a longer hospital stay, (1.7 days; 13.2 vs. 11.5; p<0.005). Patients who received IS had better functional recovery assessed with Barthel index and the Functional Ambulation Categories (FAC scale) at 3 and 6 months after the fracture. Patients with malnutrition or subtrochanteric fracture needed more tabletransfusions (p<0.005). Functional recovery at 3 and 6 months after fracture was better in patients who received intravenous iron. Neither blood transfusions nor intravenous iron were associated with infectious complications or increased mortality. The patient series of this study was compared with a group of patients with hip fracture and similar characteristics seen in 2011, before intravenous iron was available, revealing a 17% reduction in blood transfusion needs (p<0.005). CONCLUSION: The use of intravenous iron in elderly patients with hip fracture may help to reduce the number of blood units needed for the treatment of anaemia, although a causal relationship cannot be established due to not having a control group. Transfusions were associated with longer hospital stay in elderly patients with hip fracture.

First proposal of quality indicators and standards and recommendations to improve the healthcare in the Spanish National Registry of Hip Fracture.

BACKGROUND: The Spanish National Hip Fracture Registry (or Registro Nacional de Fractura de Cadera, RNFC) is a database of hip fracture patients admitted to Spanish hospitals. Its goals include assessment and continuous improvement of the care process. OBJECTIVES: To (1) establish a series of indicators, (2) evaluate their initial fulfillment, (3) propose quality standards, (4) suggest recommendations to facilitate standards compliance, and (5) monitor the indicators. METHOD: The indicators fulfilled the criteria of (1) evaluating the process or outcome, (2) being clinically relevant for patients, (3) being modifiable through changes in healthcare practice, and (4) being considered important by the RNFC participants. The first quartile obtained by the group of hospitals in each of the respective variables was proposed as the standard. The Indicators Advisory Committee (IAC) elaborated a list of recommendations for each indicator, based on the available evidence. RESULTS: Seven indicators were chosen. These indicators (its baseline compliance vs. the standard to be reached, respectively) were: the proportion of patients receiving surgery within 48h (44% vs. 63%), mobilized the first postoperative day (56% vs. 86%), with antiosteoporotic medication at discharge (32% vs. 61%), with calcium supplements at discharge (46% vs. 77%), with vitamin D supplements at discharge (67% vs. 92%), who developed pressure ulcers during hospitalization (7.2% vs. 2.1%) and with independent mobility at 30 days (58% vs. 70%). The IAC has established 25 recommendations for improving care. CONCLUSION: The indicators and standards chosen are presented, as well as the list of recommendations. This process completes the first step to improve quality of care. The results will be evaluated 6 months after implementing the recommendations.