Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
1.
Chem Asian J ; : e202400595, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39234639

RESUMEN

A preparation method for steroid-based difluoroboron complexes has been developed using lumiestrone as a steroid example. Previously inaccessible lumiestrone-based difluoroboron complexes annulated at positions 16 and 17 of the D ring have been prepared. Such difluoroboron complexes may have large synthetic potential for heterofunctionalization of steroids at the D ring. An application of a borylation mixture Ac2O-BF3•OEt2 significantly simplify the preparation of steroid "dimers" bearing two estrone moieties connected at positions 2 and 2' via a linker. Crystal structures of key representatives have been determined by X­ray diffraction.

2.
Curr Rheumatol Rev ; 20(5): 501-513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38415452

RESUMEN

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease known for causing pain, stiffness, and reduced mobility in the axial skeleton. Adalimumab, a tumor necrosis factor (TNF) inhibitor, has emerged as a promising therapeutic option for AS. METHODS: This systematic review involved a comprehensive search of randomized controlled trials related to AS treatment, conducted in major databases such as MEDLINE, Google Scholar, and PubMed. The search terms encompassed ankylosing spondylitis, adalimumab, methotrexate, other non-biologic DMARDs, glucocorticoids, NSAIDs, and analgesics. A total of 14 randomized controlled trials with 4,500 participants were included in the review. RESULTS: The review's results revealed that adalimumab demonstrated notable superiority when compared to a placebo. It effectively reduced disease activity, improved physical function, and lowered inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate. Adalimumab demonstrated a favorable safety profile, with adverse events comparable to those observed with placebo. CONCLUSION: Based on the results, adalimumab is deemed an effective treatment for AS, showcasing its potential as a first-line therapeutic option. Notably, no significant increase in adverse events was observed compared to placebo. However, the conclusion emphasizes the need for further studies with extended follow-up durations to ascertain the long-term efficacy and safety of adalimumab in AS management. This systematic review provides valuable insights supporting the use of adalimumab in the treatment of AS and underscores the importance of ongoing investigations into its long-term effects to optimize its clinical utilization in AS patients.


Asunto(s)
Adalimumab , Antirreumáticos , Espondilitis Anquilosante , Espondilitis Anquilosante/tratamiento farmacológico , Humanos , Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Materials (Basel) ; 16(22)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-38004998

RESUMEN

Using 1H NMR spectroscopy, we studied the relative mobility of the NO2 group in 1-alkyl-5-nitro-1,2,4-triazoles in the reaction of nucleophilic heterocyclic substitution by aliphatic oligoethers. The main pathways of the SNipso substitution process and the composition of resultant products from competitive reactions were examined, and the key factors influencing the relative mobility of the nitro group, such as the nitrotriazole substrate constitution, the carbon skeleton length of the O-nucleophilic agent and the process conditions, were discussed. Several independent competitive reactions directed towards the substitution of the nitro group at position C(5) in the alkyltriazole substrate by different types of nucleophiles such as alkoxide-, hydroxide- and triazolonate anions were observed to take place under conditions used. The major reaction yielded oligoethers containing terminal alkyltriazole heterocycles. Secondary reactions occurred to form the corresponding triazolone and N-C triazolyl triazolone structures in the reaction system. Additionally, in excess of the alkaline agent, alkaline hydrolysis was observed to proceed at the final stages of the process involving the O-nucleophile having a longer oligoether backbone in the series studied, leading to the formation of new O-nucleophilic sites. The obtained findings can provide a foundation for devising a method for the modification of a wide range of commercially available aliphatic oligo- or polyethers to prepare functional macromolecules whose terminals carry bioactive 1,2,4-triazole heterocycles located at a desired distance from each other.

4.
Polymers (Basel) ; 15(20)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37896341

RESUMEN

Eco-friendly polymer composites in the form of granules based on biodegradable polycaprolactone (PCL) with the inclusion of montmorillonite (MMT) from 5 to 50 wt% were prepared by solution-casting and melt extrusion. The physicochemical properties of the composite granules were studied using FTIR spectroscopy, XRDA, DSC, and TGA methods. The paper presents comparative values of crystallinity of composite granules which depend on the method of measuring (XRDA, DSC). It was shown that the crystallinity of PCL/MMT granules was affected by the preparation method and by the MMT content, and that with increase in MMT content, crystallinity increased by up to 61-67%. The change in crystallinity of the granules also affected its biodegradation in soil. At the end of exposure in soil, the mass loss for the granules prepared by solution-casting was more than 90%, whereas for the composite granules prepared by extrusion it was less than 60%. Applying melt extrusion enabled obtaining intercalated composites with predictable features, whereas only mixed-structure microcomposites could be prepared by solution-casting.

5.
Molecules ; 28(10)2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37241844

RESUMEN

The purpose of this work was to study the qualitative and quantitative composition of the main groups of biologically active substances in the fresh fruits of five different varieties of black chokeberry (Aronia melanocarpa (Michx.) Elliot), carried out within the framework of the search for available and cost-effective raw materials for food product fortification. Samples of aronia chokeberry were grown at the Federal Scientific Center named after I.V. Michurin in the Tambov region of Russia. Using a modern chemical-analytical methodology, the contents and profiles of anthocyanin pigments, proanthocyanidins, flavonoids, hydroxycinnamic acids, organic acids (malic, quinic, succinic, and citric), monosaccharides, disaccharides, and sorbitol were determined in detail. Based on the results of the study, the most promising varieties were determined in terms of the content of the main biologically active substances.


Asunto(s)
Photinia , Proantocianidinas , Polifenoles , Flavonoides , Antocianinas , Extractos Vegetales , Frutas
6.
Polymers (Basel) ; 14(24)2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36559848

RESUMEN

The degradation pattern of bacterial poly-3-hydroxybutyrate (PHB) in dimethylformamide (DMF) and dioxane solutions at 100 °C assisted by ethylenediamine, 1,4-diaminobutane and monoaminoethanol was studied. When diamines were introduced into the PHB solution in DMF in the amount of 1 mol of the reagent to 5 or 10 mol of PHB monomers, a rapid decrease in the molecular weight of the polymer was observed. The initial value of the weight average molecular weight (Mw) 840 kDa had decreased by 20-30 times within the first 10-20 min of the experiment, followed by its gradual decrease to several thousand Da. When a similar molar quantity of aminoethanol was added, the molecular weight decreased slower. PHB had been degrading much slower in the dioxane solution than in DMF. By varying the number of reagents, it was possible to reach stabilization of the Mw at 1000-3000 Da when using diamines and 8000-20,000 Da using aminoethanol. 1H NMR analysis of the oligomers revealed of amino and amido groups forming in their structure. From the opposite end of the polymer chain, residues of 3-hydroxybutyric, crotonic and isocrotonic acids were formed during degradation. Differential scanning calorimetry indicated that after oligomerization there was a decrease in the melting point from 178 °C to 140-170 °C depending on the decrease in the molecular weight. The method proposed can be used for obtaining aminated PHB oligomers.

7.
Materials (Basel) ; 15(19)2022 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-36234276

RESUMEN

An N-glycidyl-5-aminotetrazole homopolymer was synthesized herein by nucleophilic substitution of 5-aminotetrazole heterocycles for chlorine atoms in poly-(epichlorohydrin)-butanediol. Copolymers of N-glycidyl-5-aminotetrazole and glycidyl azide with a varied ratio of energetic elements were synthesized by simultaneously reacting the 5-aminotetrazole sodium salt and the azide ion with the starting polymeric matrix. The 5-aminotetrazole-based homopolymer was nitrated to furnish a polymer whose macromolecule is enriched additionally with energy-rich terminal ONO2 groups and nitrate anions. The structures of the synthesized polymers were characterized by 1H and 13C NMR and IR spectroscopies, elemental analysis and gel-permeation chromatography. The densities were experimentally measured, and thermal stability data were acquired by differential scanning calorimetry. The insertion of aminotetrazole heterocycles into the polymeric chain and their modification via nitration provides an acceptable thermal stability and a considerable enhancement in density and nitrogen content compared to azide homopolymer GAP. By the 1.3-dipolar cycloaddition reaction, we demonstrated the conceptual possibility of preparing spatially branched, energy-rich polymeric binders bearing 5-aminotetrazole and 1,2,3-triazole heterocycles starting from the plasticized azide copolymers. The presence of the aforesaid advantages makes the reported polymers attractive candidates for use as a scaffold of energetic binders.

8.
Materials (Basel) ; 15(17)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36079483

RESUMEN

To find out whether Al2O3 nanofiller is effective in improving the characteristics of polymer composites, composite polymer films based on biodegradable polylactide and epoxidized aluminum oxide nanofibers were obtained by solution casting. Surface morphology, mechanical and thermal properties of composites were studied by SEM, IR-Fourier spectroscopy, DSC and DMA. It was shown that, below and above the percolation threshold, the properties of the films differ significantly. The inclusion of alumina nanoparticles up to 0.2% leads to a plasticizing effect, a decrease in the crystallization temperature and the melting enthalpy and an increase in the tensile stress. An increase in the content of alumina nanoparticles in films above the percolation threshold (0.5%) leads to a decrease in the crystallinity of the films, an increase in stiffness and a drop in elasticity. Finding the percolation threshold of alumina nanoparticles in PLA films makes it possible to control their properties and create materials for various applications. The results of this study may have major significance for the commercial use of aluminum oxide nanofibers and can broaden the research field of composites.

9.
J Sex Marital Ther ; 48(6): 607-627, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35166643

RESUMEN

Little is known about specific intimacy dimensions' role in sexual function. In the current study, we aimed to gain more insight into how expression of feelings and sexual self-disclosure (a mediator) might potentially affect sexual functioning testing a theoretically based moderated mediation model, that uses gender as a moderator. A total of 661 participants, of which 211 were men (31,90%) and 450 were women (68,10%) aged 18-74 years involved in a monogamous committed relationship participated in the study. We used macro PROCESS 3.2 for IBM - SPSS to test simple mediation and moderated mediation models. The data revealed a significant overall effect of expression of feelings on sexual function, supporting that sexual self-disclosure mediates this relationship. We found that gender does not moderate either the relationship between expression of feelings and sexual self-disclosure nor the trajectory between sexual self-disclosure and sexual function. Our results highlight the importance of taking an interpersonal behavioral approach to sexual function, namely one that focuses on communication behaviors. However, these results need to be explored with clinical samples to understand their full potential for clinical interventions within a behavioral paradigm to partnered people's sexual problems.


Asunto(s)
Revelación , Relaciones Interpersonales , Femenino , Humanos , Masculino , Autorrevelación , Conducta Sexual , Parejas Sexuales
10.
Materials (Basel) ; 15(3)2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35161066

RESUMEN

The regularities and synthetic potentialities of the alkylation of 4(5)-nitro-1,2,3-triazole in basic media were explored, and new energetic ionic and nitrotriazole-based coordination compounds were synthesized in this study. The reaction had a general nature and ended with the formation of N1-, N2-, and N3-alkylation products, regardless of the conditions and reagent nature (alkyl- or aryl halides, alkyl nitrates, dialkyl sulfates). This reaction offers broad opportunities for expanding the variability of substituents on the nitrotriazole ring in the series of primary and secondary aliphatic, alicyclic, and aromatic substituents, which is undoubtedly crucial for solving the problems related to both high-energy materials development and medicinal chemistry when searching for new efficient bioactive compounds. An efficient methodology for the separation of regioisomeric N-alkyl(aryl)nitrotriazoles has been devised and relies on the difference in their basicity and reactivity during quaternization and complexation reactions. Based on the inaccessible N3-substitution products that exhibit a combination of properties of practical importance, a series of energy-rich ionic systems and coordination compounds were synthesized that are gaining ever-increasing interest for the chemistry of energy-efficient materials, coordination chemistry, and chemistry of ionic liquids.

11.
Polymers (Basel) ; 12(9)2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32872270

RESUMEN

Porous films have been prepared from degradable polymers-poly-3-hydroxybutyrate (PHB), poly-ε-caprolactone (PCL) and a blend of these polymers (1:3)-by adding porogen (camphor) to the polymer solution at 10%, 30% or 50% of the total mass of the polymer and porogen, and leaching it out afterwards. After the rinse, camphor content in films decreased to about 0.025%. The structure, physical/mechanical and biological properties of the films were investigated as dependent on their composition and porosity, which varied depending on the amount of camphor added. The surface of PHB films was porous, the PCL films were relatively smooth, and the PHB/PCL films had an intermediate structure. The addition of camphor increased the thickness (from 35 to 45 µm, from 40 to 80 µm and from 20 to 65 µm for PHB, PCL and PHB/PCL, respectively) and porosity (from 4.2(±3.6)% to 50.0(±12.8)%, from 6.4(±5.5)% to 54.5(±6.0)% and from 4.9(±4.8)% to 51.5(±5.8)%, respectively) of the films. The introduction (and removal) of 10% camphor into the PHB and PHB/PCL films led to an approximately twofold increase in the polar component of the free surface energy (from 5.4 ± 0.38 to 11.8 ± 1.33 and from 2.7 ± 0.13 to 5.2 ± 0.09 mN/m, respectively) but in other cases, on the contrary, a decrease in this indicator was registered. The increase of camphor addition from 0% to 50% gradually impaired mechanical properties of the films: so, Young's modulus decreased from 3.6 to 1.8 GPa, from 0.30 to 0.12 GPa and from 0.50 to 0.20 GPa for PHB, PCL and PHB/PCL, respectively. At the same time, the water vapor transmission rate considerably increased from 197.37 ± 23.62 to 934.03 ± 114.34 g/m2/d for PHB films; from 1027.99 ± 154.10 to 7014.62 ± 280.81 g/m2/d for PCL films; and from 715.47 ± 50.08 to 4239.09 ± 275.54 g/m2/d for PHB/PCL films. Results of biocompatibility testing in the culture of NIH 3T3 mouse fibroblast cells showed that for the most of experimental samples cell adhesion and proliferation were comparable or superior to the corresponding parameters on the initial nonporous films. The best results were obtained for PHB films where at Day 3 of the experiment the registered cell density for experimental samples arrived at 2.66(±0.26) × 105 cells/cm2 versus 1.29(±0.33) × 105 cells/cm2 in the control. So, the proposed method can be used to construct highly porous cell scaffolds for cellular engineering.

12.
Medchemcomm ; 10(11): 1871-1874, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32952993

RESUMEN

This review is about the significance of the use of lipidomic analysis for identifying susceptibility to skin diseases. Exactly this article describes the use of lipidomic analysis in different studies to detect abnormalities in the lipid composition of the skin to diagnose and prevent various dermatological diseases.

13.
PLoS One ; 12(6): e0178983, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28594940

RESUMEN

Mesenchymal stromal cells (MSC) have strong immunomodulatory properties and therefore can be used to control inflammation and tissue damage. It was suggested recently that MSC injections can be used to treat multi-drug resistant tuberculosis (TB). However, MSC trafficking and immunomodulatory effects of MSC injections during Mycobacterium tuberculosis (Mtb) infection have not been studied. To address this issue we have analyzed MSC distribution in tissues and local immunological effects of MSC injections in Mtb infected and uninfected mice. After intravenous injection, MSC accumulated preferentially in the lungs where they were located as cell aggregates in the alveolar walls. Immunological analysis of MSC effects included detection of activated, IFN-γ and IL-4 producing CD4+ lymphocytes, the frequency analysis of dendritic cells (CD11c+F4/80) and macrophages (CD11c-F4/80+) located in the lungs, the expression of IA/IE and CD11b molecules by these cells, and evaluation of 23 cytokines/chemokines in lung lysates. In the lungs of uninfected mice, MSC transfer markedly increased the percentage of IFN-γ+ CD4+ lymphocytes and dendritic cells, elevated levels of IA/IE expression by dendritic cells and macrophages, augmented local production of type 2 cytokines (IL-4, IL-5, IL-10) and chemokines (CCL2, CCL3, CCL4, CCL5, CXCL1), and downregulated type 1 and hematopoietic cytokines (IL-12p70, IFN-γ, IL-3, IL-6, GM-CSF). Compared to uninfected mice, Mtb infected mice had statistically higher "background" frequency of activated CD69+ and IFN-γ+ CD4+ lymphocytes and dendritic cells, and higher levels of cytokines in the lungs. The injections of MSC to Mtb infected mice did not show statistically significant effects on CD4+ lymphocytes, dendritic cells and macrophages, only slightly shifted cytokine profile, and did not change pathogen load or slow down TB progression. Lung section analysis showed that in Mtb infected mice, MSC could not be found in the proximity of the inflammatory foci. Thus, in healthy recipients, MSC administration dramatically changed T-cell function and cytokine/chemokine milieu in the lungs, most likely, due to capillary blockade. But, during Mtb infection, i.e., in the highly-inflammatory conditions, MSC did not affect T-cell function and the level of inflammation. The findings emphasize the importance of the evaluation of MSC effects locally at the site of their predominant post-injection localization and question MSC usefulness as anti-TB treatment.


Asunto(s)
Pulmón/inmunología , Células Madre Mesenquimatosas/fisiología , Tejido Adiposo , Animales , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiocina CCL3/metabolismo , Quimiocina CCL4/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CXCL1/metabolismo , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Ratones , Ratones Endogámicos C57BL , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Tuberculosis Resistente a Múltiples Medicamentos/inmunología
14.
J Gen Intern Med ; 28(12): 1581-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23733374

RESUMEN

BACKGROUND: The U.S. Preventive Services Task Force has released new guidelines on obesity, urging primary care physicians to provide obese patients with intensive, multi-component behavioral interventions. However, there are few studies of weight loss in real world nonacademic primary care, and even fewer in largely racial/ethnic minority, low-income samples. OBJECTIVE: To evaluate the recruitment, intervention and replications costs of a 2-year, moderate intensity weight loss and blood pressure control intervention. DESIGN: A comprehensive cost analysis was conducted, associated with a weight loss and hypertension management program delivered in three community health centers as part of a pragmatic randomized trial. PARTICIPANTS: Three hundred and sixty-five high risk, low-income, inner city, minority (71 % were Black/African American and 13 % were Hispanic) patients who were both hypertensive and obese. MAIN MEASURES: Measures included total recruitment costs and intervention costs, cost per participant, and incremental costs per unit reduction in weight and blood pressure. KEY RESULTS: Recruitment and intervention costs were estimated $2,359 per participant for the 2-year program. Compared to the control intervention, the cost per additional kilogram lost was $2,204 /kg, and for blood pressure, $621 /mmHg. Sensitivity analyses suggest that if the program was offered to a larger sample and minor modifications were made, the cost per participant could be reduced to the levels of many commercially available products. CONCLUSIONS: The costs associated with the Be Fit Be Well program were found to be significantly more expensive than many commercially available products, and much higher than the amount that the Centers for Medicare and Medicaid reimburse physicians for obesity counseling. However, given the serious and costly health consequences associated with obesity in high risk, multimorbid and socioeconomically disadvantaged patients, the resources needed to provide interventions like those described here may still prove to be cost-effective with respect to producing long-term behavior change.


Asunto(s)
Centros Comunitarios de Salud/economía , Obesidad/economía , Obesidad/terapia , Aptitud Física , Pérdida de Peso , Programas de Reducción de Peso/economía , Adulto , Anciano , Costos y Análisis de Costo/economía , Costos y Análisis de Costo/métodos , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/economía , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Selección de Paciente , Aptitud Física/fisiología , Pérdida de Peso/fisiología , Programas de Reducción de Peso/métodos
15.
Cancer Discov ; 3(1): 96-111, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23125191

RESUMEN

UNLABELLED: Persistent signaling by the oncogenic EGF receptor (EGFR) is a major source of cancer resistance to EGFR targeting. We established that inactivation of 2 sterol biosynthesis pathway genes, SC4MOL (sterol C4-methyl oxidase-like) and its partner, NSDHL (NADP-dependent steroid dehydrogenase-like), sensitized tumor cells to EGFR inhibitors. Bioinformatics modeling of interactions for the sterol pathway genes in eukaryotes allowed us to hypothesize and then extensively validate an unexpected role for SC4MOL and NSDHL in controlling the signaling, vesicular trafficking, and degradation of EGFR and its dimerization partners, ERBB2 and ERBB3. Metabolic block upstream of SC4MOL with ketoconazole or CYP51A1 siRNA rescued cancer cell viability and EGFR degradation. Inactivation of SC4MOL markedly sensitized A431 xenografts to cetuximab, a therapeutic anti-EGFR antibody. Analysis of Nsdhl-deficient Bpa(1H/+) mice confirmed dramatic and selective loss of internalized platelet-derived growth factor receptor in fibroblasts, and reduced activation of EGFR and its effectors in regions of skin lacking NSDHL. SIGNIFICANCE: This work identifies a critical role for SC4MOL and NSDHL in the regulation of EGFR signaling and endocytic trafficking and suggests novel strategies to increase the potency of EGFR antagonists in tumors.


Asunto(s)
3-Hidroxiesteroide Deshidrogenasas/genética , Receptores ErbB/metabolismo , Oxigenasas de Función Mixta/genética , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Cetuximab , Colesterol/metabolismo , Endocitosis , Receptores ErbB/antagonistas & inhibidores , Humanos , Masculino , Ratones , Ratones SCID , Ratones Transgénicos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Transporte de Proteínas
16.
Transl Behav Med ; 1(3): 427-435, 2011 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-22081776

RESUMEN

Information on cost-effectiveness of multiple-risk-factor lifestyle interventions for Latinas with diabetes is lacking. The aim of this paper is to evaluate costs and cost-effectiveness for ¡Viva Bien!, a randomized trial targeting Latinas with type 2 diabetes. We estimated 6-month costs; calculated incremental costs per behavioral, biologic, and quality-of-life change; and performed sensitivity analyses from health plan and participant perspectives. Recruitment, intervention, and participant costs were estimated at $45,896, $432,433, and $179,697, respectively. This translates to $4,634 in intervention costs per ¡Viva Bien! participant; $7,723 in both per unit reduction in hemoglobin A1c and per unit reduction in body mass index. Although costs may be higher than interventions that address one risk factor, potential risks for longer-term health-care costs are high for this at-risk group. Given the benefits of ¡Viva Bien!, cost reductions are recommended to enhance its efficiency, adoption, and long-term maintenance without diluting its effectiveness.

17.
Perm J ; 15(2): 15-22, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21841920

RESUMEN

OBJECTIVE: Current pediatric well-child care (WCC) may be inefficient and inadequate with respect to primary care physicians' abilities to deliver prescribed preventive and developmental services. New Internet-related technologies may improve the efficiency and effectiveness of WCC. This article examines the potential resource cost implications associated with a change in the delivery model of WCC in a capitated, integrated managed care system. STUDY DESIGN: Decision analyses and Monte Carlo simulations were used to estimate the variation in resource costs between the current WCC model and a high-performance WCC model, stratifying by age, risk level, and the proportion of pediatric members that may not seek WCC. METHODS: Demographic and health care utilization data associated with 14,910 pediatric enrollees, ages newborn to 5 years, enrolled at Kaiser Permanente Colorado were used to simulate the change in costs attributable to a change in the model of WCC. RESULTS: Simulation models and sensitivity analyses suggest that the implementation of the high-performance WCC model is likely to be relatively resource cost neutral in a managed care system. CONCLUSIONS: Preliminary findings suggest that implementation of innovative changes in WCC may allow for efficient reallocation of resources to higher-risk children in a relatively cost neutral manner. However, innovative changes that involve the use of unreimbursed non-face-to-face encounters and nonphysician health care professionals may present challenges with respect to implementation of a new model of WCC in a fee-for-service environment.

18.
Sci Signal ; 3(140): ra67, 2010 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-20858866

RESUMEN

Intrinsic and acquired cellular resistance factors limit the efficacy of most targeted cancer therapeutics. Synthetic lethal screens in lower eukaryotes suggest that networks of genes closely linked to therapeutic targets would be enriched for determinants of drug resistance. We developed a protein network centered on the epidermal growth factor receptor (EGFR), which is a validated cancer therapeutic target, and used small interfering RNA screening to comparatively probe this network for proteins that regulate the effectiveness of both EGFR-targeted agents and nonspecific cytotoxic agents. We identified subnetworks of proteins influencing resistance, with putative resistance determinants enriched among proteins that interacted with proteins at the core of the network. We found that clinically relevant drugs targeting proteins connected in the EGFR network, such as protein kinase C or Aurora kinase A, or the transcriptional regulator signal transducer and activator of transcription 3 (STAT3), synergized with EGFR antagonists to reduce cell viability and tumor size, suggesting the potential for a direct path to clinical exploitation. Such a focused approach can potentially improve the coherent design of combination cancer therapies.


Asunto(s)
Citotoxinas/metabolismo , Descubrimiento de Drogas/métodos , Resistencia a Antineoplásicos/genética , Receptores ErbB/metabolismo , Neoplasias/tratamiento farmacológico , Mapeo de Interacción de Proteínas/métodos , Transducción de Señal/genética , Aurora Quinasa A , Aurora Quinasas , Citotoxinas/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Proteína Quinasa C/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Factor de Transcripción STAT3/metabolismo
19.
Int J Behav Nutr Phys Act ; 6: 92, 2009 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-20040096

RESUMEN

BACKGROUND: The purpose of this paper is to evaluate costs associated with the online intervention trial, Making Effective Nutritional Choices for Cancer Prevention (MENU), and to connect the findings to the study outcomes. METHODS: Using prospective data collected during the MENU development and implementation phases, we estimated overall costs per person, incremental costs for the three arms of the MENU intervention, and incremental costs per change in fruit and vegetable (F&V) consumption across the studied population. The MENU study was conducted in five HMO sites of the Cancer Research Network. The number of eligible study participants who were enrolled in the study was 2,540. Recruited participants were randomized into (1) an untailored website program, (2) tailored website program, or (3) tailored web program plus personalized counseling (HOBI) via email. The primary measures for these analyses include the total intervention costs, average cost per participant, and the average cost per mean change in daily intake of F&V, stratified by study arm. RESULTS: The mean change in F&V consumption was greater in both the tailored arm and statistically higher in the HOBI arm relative to the untailored arm. The untailored arm achieved +2.34 servings increase vs. the tailored website arm (+2.68) and the HOBI arm (+2.80) servings increase. Total intervention costs for MENU participants who completed the 12-month follow-up assessment, by study arm, were estimated to be $197,197 or $110 respectively. This translates to $69 per participant in the untailored web site intervention, $81 per participant in the tailored website intervention, and $184 per participant in the HOBI intervention and a cost per average change in F&V consumption to be $35, $27 and $61 respectively. CONCLUSIONS: Providing personalized "tailored" messages and additional personalized support via email generated an additional $12-$115 per participant, over the untailored web program. Incremental increases in F&V consumption associated with the email support arm were associated with considerable increases in intervention costs, suggesting that the most cost effective arm of the MENU study by servings gained was the tailored website.

20.
Ann Behav Med ; 37(2): 218-27, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19291342

RESUMEN

BACKGROUND/PURPOSE: Cost and cost effectiveness of behavioral interventions are critical parts of dissemination and implementation into non-academic settings. Due to the lack of indicative data and policy makers' increasing demands for both program effectiveness and efficiency, cost analyses can serve as valuable tools in the evaluation process. METHODS: To stimulate and promote broader use of practical techniques that can be used to efficiently estimate the implementation costs of behavioral interventions, we propose a set of analytic steps that can be employed across a broad range of interventions. RESULTS/CONCLUSIONS: Intervention costs must be distinguished from research, development, and recruitment costs. The inclusion of sensitivity analyses is recommended to understand the implications of implementation of the intervention into different settings using different intervention resources. To illustrate these procedures, we use data from a smoking reduction practical clinical trial to describe the techniques and methods used to estimate and evaluate the costs associated with the intervention. Estimated intervention costs per participant were $419, with a range of $276 to $703, depending on the number of participants.


Asunto(s)
Terapia Conductista/economía , Medicina de la Conducta/métodos , Costos de la Atención en Salud , Evaluación de Programas y Proyectos de Salud/métodos , Cese del Hábito de Fumar/métodos , Adolescente , Adulto , Anciano , Terapia Conductista/métodos , Medicina de la Conducta/economía , Análisis Costo-Beneficio/métodos , Humanos , Persona de Mediana Edad , Educación del Paciente como Asunto/economía , Educación del Paciente como Asunto/métodos , Evaluación de Programas y Proyectos de Salud/economía , Cese del Hábito de Fumar/economía , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA