Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy: Study protocol of a cluster randomized clinical trial (Multi-PAP project)

Background: Multimorbidity is associated with negative effects both on people''s health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (=3 chronic diseases) and polypharmacy (=5 drugs prescribed in =3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT0286679

Postoperative outcomes after minimally invasive esophagectomy: an international cohort study from the Oesophagogastric Anastomosis Audit (OGAA)

ObjectiveTo compare the postoperative pulmonary complications (PPC) after minimally invasive or open transthoracic esophagectomy for esophageal cancer in an international, multicenter cohort.Summary of background dataOngoing debate exists around the optimal surgical approach for esophageal cancer, with limited data assessing the external validity of randomised trials on outcomes of MIEMethodsPatients undergoing open (OE, n = 744), hybrid (HE, n = 500), and totally minimally invasive esophagectomy (TMIE, n = 540) for esophageal cancer were identified from the international, prospective Oesophagogastric Anastomosis Audit (OGAA). Multivariable models were used to investigate PPC (primary outcome) as well as overall complications, major complications, anastomotic leak and 90-day mortality (secondary outcomes).ResultsPPC rates were lower after TMIE compared to OE and HE (28% vs 37% vs 39%, p = 0.002), even on adjusted analyses compared to OE (odds ratio (OR): 0.60, CI95%: 0.45-0.78). TMIE was also associated with significantly lower overall complications (OR: 0.68, CI95%: 0.52-0.88) compared to OE, but not for major complications (OR: 0.90, CI95%: 0.67-1.21), anastomotic leak (OR: 1.39, CI95%: 0.96-2.01) and 90-day mortality (OR: 0.49, CI95%: 0.22-1.04). Sensitivity analyses by underlying respiratory disease, neoadjuvant chemoradiotherapy or high-volume centers confirmed above findings.ConclusionThis study provides real-world data that TMIE was associated with lower 90-day PPC than OE and HE approaches, especially in patients with underlying respiratory disease or receiving neoadjuvant chemoradiotherapy. These warrant a further review into causes and mechanisms in selected patients, and that quality assurance in delivery of TMIE is probably of major importance. The ideal surgical approach remains unclear, and ongoing trials will provide more evidence within a few years that may clarify the optimum approach to locally advanced esophageal cancers

Calidad de planta de Cedrela odorata L. asociada con prácticas culturales de vivero

En México muchas reforestaciones con Cedrela odorata no han tenido un desempeño inicial favorable, principalmente por el uso de planta de baja calidad, por lo que se requieren de alternativas en los viveros forestales que mejoren dicha condición. En el presente trabajo fue examinada la influencia del volumen de envase e hidrogel sobre la morfología, estado nutrimental y desempeño en campo de plántulas de C. odorata. El volumen del envase se manejó a dos niveles: bolsa de polietileno de 500 mL y tubete de plástico de 380 mL; el hidrogel, con tres niveles: adición de 0, 2 y 4 g L-1 de sustrato. Las características de las plántulas se evaluaron en vivero, mediante la determinación de varios indicadores morfológicos de calidad de planta y el uso de nomogramas de análisis de vectores para el diagnóstico del estado del nitrógeno, fósforo y potasio. El desempeño en campo fue medido como supervivencia y crecimiento durante 17 meses, a partir del establecimiento de la plantación. Las plántulas con los mejores atributos fueron las producidas en envases de 500 mL con la adición de hidrogel al sustrato en dosis de 4 g L-1; no obstante, el mejor desempeño en campo correspondió a las producidas en envases de 500 mL sin hidrogel, lo que permite concluir que el volumen de envase tiene un efecto directo en la calidad de planta de C. odorata

New Tacrine–4-Oxo-4<i>H</i>-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer’s disease (AD), a new family of tacrine–4-oxo-4<i>H</i>-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4<i>H</i> -chromene was chosen for its radical capture and β-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine–4-oxo-4<i>H</i>-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- <i>N</i>-{10-[(1,2,3,4-tetrahydroacridin-9-yl)­amino]­decyl}-4 <i>H</i>-chromene-2-carboxamide (<b>19</b>) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties

Facile Synthesis of Gold(III) Aryl–Carbene Metallacycles

New gold­(III) metallacyclic complexes with unprecedented aryl–carbene bidentate ligands have been prepared by the reaction of the cycloaurated gold­(III) complex [AuCl₂(pap-C¹,N)] (pap = 2-(2-pyridylamino)­phenyl) with isocyanide CNR (R = 2-naphthyl (<b>1</b>), cyclohexyl (<b>2</b>), or 2,6-dimethylphenyl (<b>3</b>)). Complexes have been spectroscopically and structurally characterized, showing in some complexes aurophilic gold­(III)···gold­(III) and π–π interactions. In contrast with the starting material these complexes are emissive in the solid state, probably because of the better σ-donor properties of the new bidentate ligands

Dynamic Structure and Subsurface Oxygen Formation of a Working Copper Catalyst under Methanol Steam Reforming Conditions: An <i>in Situ</i> Time-Resolved Spectroscopic Study

The dynamic behavior of a CuO/ZnO/Ga2O3 catalyst under methanol steam reforming (MSR) reaction conditions promoted by a high dispersion of the copper nanoparticles and defect sites of a nonstoichiometric ZnGa2O4 spinel phase has been observed, where structural changes taking place in the initial state of the reaction determine the final state of the catalyst in stationary reaction conditions. Mass spectrometry (MS) studies under transient conditions coupled to X-ray photoelectron spectroscopy (XPS) have shown copper oxidation to Cu+ in the initial state of the reaction (TOS = 4 min), followed by a fast reduction of the outer shell to Cu0, while keeping dissolved oxygen species in the inner layers of the nanoparticle. The presence of this subsurface oxygen impairs a positive charge to the uppermost surface copper species, that is, Cuδ+, which undoubtedly plays an important role on the MSR catalytic activity. The detection of these features, unperceived by conventional spectroscopic and catalytic studies, has only been possible by combining synchrotron NAP-XPS studies with transient studies performed in a low volume catalytic reactor connected to MS and linked with Raman and laboratory scale XPS studies