Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017

In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the “social subsidy”), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries’ out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud

Prevalence of cognitive impairment in a high social risk population older than 60 years from Neuquén capital

Introducción: La información que existe sobre demencia y deterioro cognitivo es escasa en Argentina, y particularmente en la Patagonia. Objetivo y Métodos: El objetivo del estudio fue determinar la prevalencia de deterioro cognitivo. Se realizó una encuesta puerta a puerta a todas las personas mayores de 60 años que vivían en un barrio de la ciudad de Neuquén de alto riesgo social, donde se evaluaban variables geriátricas y cognitivas, incluyéndose un Mini-Mental, Test del Reloj y un Set test según el nivel de instrucción. Resultados: De las 78 encuestas evaluadas, la media de edad fue de 70,75 años, 37 de sexo femenino, con una escolaridad promedio de 4,37 años, con un 33% de personas analfabetas funcionales. Se evidenció deterioro cognitivo en 29,49% de los pacientes, siendo más elevado a mayor edad y menor nivel de instrucción. Conclusiones: La prevalencia de deterioro cognitivo en la población estudiada fue más elevada que en otros estudios argentinos asociado a un porcentaje de analfabetismo más alto que en otras jurisdicciones.Introduction: The information that exists on dementia and cognitive impairment is scarce in Argentina, particularly in Patagonia. Objective and Methods: The aim of the study was to determine the prevalence of cognitive impairment. A door to door survey was performed to all people over 60 who lived in a high social risk neighborhood in Neuquen city, where geriatric and cognitive variables were evaluated, including Folstein Mini-Mental State Examination, clock test and test set according to the level of instruction. Results: Of the 78 surveys assessed, the mean age was 70.75 years, 37 female, with an average of 4.37 years of schooling, with 33% of functional illiterates. Cognitive impairment was evidenced in 29.49%, being high er at older and less educated respondents. Conclusions: The prevalence of cognitive impairment in the study population was higher than in other Argentine studies associated with an illiteracy rate higher than in other jurisdictions.Facultad de Ciencias Médica

Understanding stability trends along the lanthanide series

[Abstract] The stability trends across the lanthanide series of complexes with the polyaminocarboxylate ligands TETA4− (H4TETA=2,2′,2′′,2′′′‐(1,4,8,11 tetraazacyclotetradecane‐1,4,8,11‐tetrayl)tetraacetic acid), BCAED4− (H4BCAED=2,2′,2′′,2′′′ {[(1,4‐diazepane‐1,4‐diyl)bis(ethane‐2,1‐diyl)]bis(azanetriyl)}tetraacetic acid), and BP18C62− (H2BP18C6=6,6′‐[(1,4,10,13‐tetraoxa‐7,16‐diazacyclooctadecane‐7,16 diyl)bis(methylene)]dipicolinic acid) were investigated using DFT calculations. Geometry optimizations performed at the TPSSh/6‐31G(d,p) level, and using a 46+4fn ECP for lanthanides, provide bond lengths of the metal coordination environments in good agreement with the experimental values observed in the X‐ray structures. The contractions of the Ln3+ coordination spheres follow quadratic trends, as observed previously for different isostructural series of complexes. We show here that the parameters obtained from the quantitative analysis of these data can be used to rationalize the observed stability trends across the 4f period. The stability trends along the lanthanide series were also evaluated by calculating the free energy for the reaction [La(L)]n+/−(sol)+Ln3+(sol)→[Ln(L)]n+/ (sol)+La3+(sol). A parameterization of the Ln3+ radii was performed by minimizing the differences between experimental and calculated standard hydration free energies. The calculated stability trends are in good agreement with the experimental stability constants, which increase markedly across the series for BCAED4−complexes, increase smoothly for the TETA4− analogues, and decrease in the case of BP18C62− complexes. The resulting stability trend is the result of a subtle balance between the increased binding energies of the ligand across the lanthanide series, which contribute to an increasing complex stability, and the increase in the absolute values of hydration energies along the 4f period.Xunta de Galicia; CN2012/01

Use of medication in elderly people don’t institutionalized

El uso inadecuado de medicamentos en el adulto mayor representa un problema de salud pública en constante progresión. Realizamos un estudio de utilización de medicamentos de tipo transversal, empleando una encuesta autoadministrada para evaluar el uso de medicamentos y la prescripción inadecuada en adultos mayores ambulatorios de la ciudad de La Plata, Argentina, en 2009. El total de personas encuestadas fue de 215. El promedio de medicamentos usados por persona fue 3,19 ± 2,02, la polimedicación estuvo presente en 24,1 % de los sujetos. Recibieron medicamentos potencialmente inapropiados (MPI) el 25,5 %, 31,9 % y 30,0 % de los pacientes, según los criterios Beers, lista PRISCUS, y criterios STOPP, respectivamente. Esta investigación constató que la prescripción potencialmente inapropiada es frecuente y que existe una necesidad creciente de contar con un listado de medicamentos potencialmente inapropiados, adecuada a cada realidad, que contemple aquellas situaciones donde el tratamiento es subóptimo.Misuse of drugs in the elderly is a rampant public health problem. We conducted a cross-sectional study using a selfadministered survey to assess drug use and inadedequate prescription among noninstotunilazed elderly patients in the city of La Plata, Argentina in 2009. The total number of respondents was 215. The average number of drugs used per person was 3.19 ± 2.02, polypharmacy was present in 24.1 % of subjects. Potentially inappropriate medications (MPI) were given in 25.5 %, 31.9 % and 30.0 % of the patients, according to Beers criteria, Priscus list, and STOPP criteria, respectively. This research found that potentially inappropriate prescribing is common and there is a growing need for a list of potentially inappropriate medications, as appropriate to each situation, that considers situations where treatment is suboptimal.Facultad de Ciencias Médica

Efficacy of platelet-rich plasma applied to post-extraction retained lower third molar alveoli. A systematic review

Dental retentions have a high prevalence among the general population and their removal can involve multiple complications. The use of platelet rich plasma has been proposed in an attempt to avoid these complications, as it contains high growth factors and stimulates diverse biological functions that facilitate the healing of soft and hard tissues. Objectives: To evaluate the available scientific evidence related to the application of platelet-rich plasma in the post-extraction alveoli of a retained lower third molars. Material and Methods: A systematic review of published literature registered in the Medline, EMBASE, Cochrane and NIH databases. The following categories were included: human randomized clinical studies. Key search words were: platelet rich plasma; platelet rich plasma and oral surgery; platelet rich in growth factors and third molar. Results: Of 101 potentially valid articles, seven were selected, of which four were rejected as they failed to meet quality criteria. Three studies fulfilled all selection and quality criteria: Ogundipe et al.; Rutkowski et al.; Haraji et al. The studies all measured osteoblast activity by means of sintigraphy, and also registered pain, bleeding, inflammation, temperature, numbness as perceived by the patients, radiological bone density and the incidence of alveolar osteitis. Conclusions: Scientific evidence for the use of PRP in retained third molar surgery is poor. For this reason rando - mized clinical trials are needed before recommendations for the clinical application of PRP can be made

Magnetic anisotropies in rhombic lanthanide(III) complexes do not conform to Bleaney’s theory

[Abstract] We report a complete set of magnetic susceptibilities of lanthanide complexes with a macrocyclic ligand based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing four hydroxyethyl pendant arms (L1). The [LnL1]3+ complexes are isostructural along the lanthanide series from Ce3+ to Yb3+, with the only structural change observed along the series being the monotonous shortening of the Ln–donor distances due to lanthanide contraction. The 1H NMR spectra point to a D2 symmetry of the [LnL1]3+ complexes in aqueous solution, which provides a unique opportunity for analysis of the rhombic magnetic anisotropies with an unequivocal location of the magnetic axes. The contact contributions for the observed paramagnetic shifts have been estimated with density functional theory calculations on the [GdL1]3+ complex. Subsequently, the pseudocontact shifts could be factored out, thereby giving access to the axial and rhombic contributions of the magnetic susceptibility tensor. Our results show that the calculated magnetic anisotropies do not follow the trends predicted by Bleaney’s theory, particularly in the case of Ho3+ and Er3+ complexes.Ministerio de Economía y Competitividad; CTQ2013-43243-PMinisterio de Ciencia e Innovación; CTQ2011-2448

Water exchange rates and mechanisms in tetrahedral [Be(H2O)4]2+ and [Li(H2O)4]+ complexes using DFT methods and cluster‐continuum models

[Abstract] The water exchange reactions in aquated Li+ and Be2+ ions were investigated with density functional theory calculations performed using the [Li(H2O)4]+·14H2O and [Be(H2O)4]2+·8H2O systems and a cluster‐continuum approach. A range of commonly used functionals predict water exchange rates several orders of magnitude lower than the experimental ones. This effect is attributed to the overstabilization of coordination number four by these functionals with respect to the five‐coordinated transition states responsible for the associative (A) or associative interchange (Ia) water exchange mechanisms. However, the M06 and M062X functionals provide results in good agreement with the experimental data: M062X/TZVP calculations yield a concerted Iamechanism for the water exchange in [Be(H2O)4]2+·8H2O that gives an average residence time of water molecules in the first coordination sphere of 260 μs. For [Li(H2O)4]+·14H2O the water exchange reaction is predicted to follow an A mechanism with a residence time of inner‐sphere water molecules of 25 ps.Ministerio de Economía y Competitividad; CTQ2013‐43243‐PMinisterio de Economía y Competitividad; CTQ2015‐71211‐RED

Developing the family of picolinate ligands for Mn2+ complexation

[Abstract] We have reported here a series of ligands containing pentadentate 6,6′-(azanediylbis(methylene))dipicolinic acid units that differ in the substituent present at the amine nitrogen atom (acetate: H3DPAAA; phenyl: H2DPAPhA; dodecyl: H2DPAC12A; 4-hexylphenyl: H2DPAC6PhA). The protonation constants of the hexadentate DPAAA3− and pentadentate DPAPhA2−ligands and the stability constants of their Mn2+ complexes were determined using pH-potentiometry (25 °C, 0.15 M NaCl). The mono-hydrated [Mn(DPAAA)]− complex (logKMnL = 13.19(5)) was found to be considerably more stable than the bis-hydrated [Mn(DPAPhA)] analogue (logKMnL = 9.55(1)). A detailed 1H and 17O NMR relaxometric study was carried out to determine the parameters that govern the proton relaxivities of these complexes. The [Mn(DPAC12A)] complex, which contains a dodecyl lipophilic chain, forms micelles in solution characterized by a critical micellar concentration (cmc) of 96(9) μM. The lipophilic [Mn(DPAC6PhA)] and [Mn(DPAC12A)] derivatives form rather strong adducts with Human Serum Albumin (HSA) with association constants of 7.1 ± 0.1 × 103 and 1.3 ± 0.4 × 105 M−1, respectively. The X-ray structure of the complex {K(H2O)4}{[Mn(DPAAA)(H2O)]}2 shows that the Mn2+ ion in [Mn(DPAAA)]− is coordinated to the six donor atoms of the ligand, a coordinated water molecule completing the pentagonal bipyramidal coordination environment.Ministerio de Economía y Competitividad; CTQ2015-71211-REDTMinisterio de Economía y Competitividad; CTQ2016-76756-

Density functional dependence of molecular geometries in lanthanide(III) complexes relevant to bioanalytical and biomedical applications

[Abstract] A set of 15 lanthanide-containing model systems was used to evaluate the performance of 15 commonly available density functionals (SVWN, SPL, BLYP, G96LYP, mPWLYP, B3LYP, BH&HLYP, B3PW91, BB95, mPWB95, TPSS, TPSSh, M06, CAM-B3LYP and wB97XD) in geometry determination, benchmarked against MP2 calculations. The best agreement between DFT optimized geometries and those obtained from MP2 calculations is provided by meta-GGA and hybrid meta-GGA functionals. The use of hybrid-GGA functionals such as BH&HLYP and B3PW91 also provide reasonably good results, while B3LYP provides an important overestimation of the metal–ligand bonds. The performance of different basis sets to describe the ligand(s) atoms, as well as the use of large-core (LC) RECPs and small-core (SC) RECPs, has been also assessed. Our calculations show that SCRECP calculations provide somewhat shorter GdIII–donor distances than the LCRECP approach, the average contraction of bond distances for the systems investigated amounting to 0.033 Å. However, geometry optimizations with the SCRECP (in combination with the mPWB95 functional and the 6-31G(d) basis set for the ligand atoms) take about 15 times longer than the LC counterparts, and about four times longer than MP2/LCRECP/6-31G(d) calculations. The 6-31G(d), 6-311G(d), 6-311G(d,p) or cc-pVDZ basis sets, in combination with LCRECPs, appear to offer an adequate balance between accuracy and computational cost for the description of molecular geometries of LnIII complexes. Electronic energies calculated with the the cc-pVxZ family (x = D-6) indicate a relative fast convergence to the complete basis set (CBS) limit with basis set size. The inclusion of bulk solvent effects (IEFPCM) was shown to provoke an important impact on the calculated geometries, particularly on the metal–nitrogen distances. Calculations performed on lanthanide complexes relevant for practical applications confirmed the important effect of the solvent on the calculated geometries.Ministerio de Educación y Ciencia; CTQ2009-10721Xunta de Galicia; IN845B-2010/06

Applications of density functional theory (DFT) to investigate the structural, spectroscopic and magnetic properties of lanthanide(III) complexes

[Abstract] Density functional theory (DFT) has become a general tool to investigate the structure and properties of complicated inorganic molecules, such as lanthanide(III) coordination compounds, due to the high accuracy that can be achieved at relatively low computational cost. Herein, we present an overview of different successful applications of DFT to investigate the structure, dynamics, vibrational spectra, NMR chemical shifts, hyperfine interactions, excited states, and magnetic properties of lanthanide(III) complexes. We devote particular attention to our own work on the conformational analysis of LnIII-polyaminocarboxylate complexes. Besides, a short discussion on the different approaches used to investigate lanthanide(III) complexes, i. e. all-electron relativistic calculations and the use of relativistic effective core potentials (RECPs), is also presented. The issue of whether the 4f electrons of the lanthanides are involved in chemical bonding or not is also shortly discussed.Ministerio de Educación y Ciencia; CTQ2009-10721Xunta de Galicia; IN845B-2010/06