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1.
Public Health ; 230: 163-171, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555685

RESUMO

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.


Assuntos
Vacinas Meningocócicas , Neisseria meningitidis , Enfermeiras e Enfermeiros , Humanos , Espanha , Vacinas Conjugadas , Comportamento de Escolha , Preparações Farmacêuticas
3.
Public Health ; 167: 136-146, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30660981

RESUMO

OBJECTIVES: Herpes zoster (HZ) is an important cause of morbidity around the world, especially among the adult population aged >50 years. STUDY DESIGN: A systematic review of the literature (up to October 31, 2016) was performed to identify available evidence on incidence of HZ in the general population and in a specific subpopulation in Spain. METHODS: PubMed and Embase databases were searched, combining the following search terms: 'herpes zoster', 'diabetes mellitus (DM)', 'chronic obstructive pulmonary disease (COPD)', 'chronic heart failure', 'mental disorders' and 'immunocompromised'. Supplements for local scientific congresses, non-indexed Spanish journals and official epidemiological reports, potentially HZ related, were also manually searched. The inclusion criteria were the following: English or Spanish publications reporting incidence of HZ in the Spanish general population and/or specific subpopulations. No restrictions were applied on the study design or population age. RESULTS: Among 269 references retrieved (48 PubMed, 148 Embase and 73 manual searching), 34 were finally included. Incidence of HZ in the general population ranged from 2.1 to 5.5/1000 person-years. HZ incidence ranged from 9.4 to 15.3/1000 patients with DM and from 11.0 to 11.4/1000 population with COPD or cardiovascular disease. In asthmatic patients, 6.9 HZ cases/1000 subjects were reported. The highest HZ incidence (1.3-400.0/1000 person-years) was in immunocompromised persons (10.0/1000 patients with cancer, 12.5/1000 patients with AIDS, from 5.0 to 240.0/1000 transplanted patients and from 6.6 to 27.0/1000 population with rheumatic diseases). Three studies estimated an increased risk of HZ in comparison with general population, for patients with DM (24%), COPD (39%) and COPD receiving inhaled corticosteroids (61%). CONCLUSIONS: The results suggest a high risk of HZ in certain age groups and specific subpopulations. This study could contribute to identify target age populations and at-risk groups if implementation of HZ vaccination programmes in Spain would be considered.


Assuntos
Herpes Zoster/epidemiologia , Humanos , Incidência , Fatores de Risco , Espanha/epidemiologia
4.
Biochim Biophys Acta Mol Basis Dis ; 1864(2): 325-337, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29109031

RESUMO

MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.


Assuntos
Apoptose , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , MicroRNAs/metabolismo , Animais , Apolipoproteínas E/genética , Ductos Biliares/cirurgia , Tetracloreto de Carbono , Proliferação de Células , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Ciclo-Oxigenase 2/genética , Regulação para Baixo , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/terapia , Camundongos , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos , Fator de Crescimento Transformador beta1/metabolismo
5.
Phys Chem Chem Phys ; 20(2): 1105-1113, 2018 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-29238771

RESUMO

An analysis of the electronic rearrangements for the oxidative addition of ammonia to a set of five representative (PXP)Ir pincer complexes (X = B, CH, O, N, SiH) is performed. We aim to understand the factors controlling the activation and reaction energies of this process by combining different theoretical strategies based on DFT calculations. Interestingly, complexes featuring higher activation barriers yield more exothermic reactions. The analysis of the reaction path using the bonding evolution theory shows that the main chemical events, N-H bond cleavage and Ir-H bond formation, take place before the transition structure is reached. Metal oxidation implies an electron density transfer from non-shared Ir pairs to the Ir-N bond. This decrement in the atomic charge of the metal provokes different effects in the ionic contribution of the Ir-X bonding depending on the nature of the X atom as shown by the interacting quantum atoms methodology.

6.
J Chem Phys ; 148(5): 054201, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29421897

RESUMO

Doppler-free saturated-absorption Lamb dips were measured at sub-Pa pressures on rovibrational lines of H216O near 7180 cm-1, using optical feedback frequency stabilized cavity ring-down spectroscopy. The saturation of the considered lines is so high that at the early stage of the ring down, the cavity loss rate remains unaffected by the absorption. By referencing the laser source to an optical frequency comb, transition frequencies are determined down to 100 Hz precision and kHz accuracy. The developed setup allows resolving highly K-type blended doublets separated by about 10 MHz (to be compared to a HWHM Doppler width on the order of 300 MHz). A comparison with the most recent spectroscopic databases is discussed. The determined K-type splittings are found to be very well predicted by the most recent variational calculations.

7.
J Environ Manage ; 212: 440-449, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29455152

RESUMO

The growing number of road vehicles is a major source of regional and global atmospheric pollution increasing concentrations of CO2 in the air, and levels of metals in air and soil. Nevertheless, the effects of these pollutants on plants growing at roadsides are poorly documented. We carried out an observational study of unmanipulated plants growing by the road, to identify the morpho-physiological responses in a perennial grass Dactylis glomerata. Firstly, we wanted to know the general effect of traffic intensity and ambient CO2 and its interactions on different plant traits. Accordingly, we analyzed the photosynthetic response by field A/Ci Response Curves, SLA, pigment pools, foliar nitrogen, carbohydrates and morphological traits in plants at three distances to the road. Secondly, we wanted to know if Dactylis glomerata plants can accumulate metals present on the roadside (Pb, Zn, Cu, and Sr) in their tissues and rhizosphere, and the effect of these metals on morphological traits. The MANCOVA whole model results shown: 1) a significant effect of road ambient CO2 concentration on morphological traits (not affected by traffic intensity, P interaction CO2 x traffic intensity>0.05), that was mainly driven by a significant negative relationship between the inflorescence number and ambient CO2; 2) a positive and significant relationship between ambient CO2 and the starch content in leaves (unaffected by traffic intensity); 3) a reduction in Jmax (electron transport rate) at high traffic intensity. These lines of evidences suggest a decreased photosynthetic capacity due to high traffic intensity and high levels of ambient CO2. In addition, Pb, Cu, Zn and Sr were detected in Dactylis glomerata tissues, and Cu accumulated in roots. Finally, we observed that Dactylis glomerata individuals growing at the roadside under high levels of CO2 and in the presence of metal pollutants, reduced their production of inflorescences.


Assuntos
Dactylis/metabolismo , Emissões de Veículos , Dactylis/crescimento & desenvolvimento , Monitoramento Ambiental , Solo , Poluentes do Solo/farmacocinética
8.
J Viral Hepat ; 24(9): 750-758, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28273410

RESUMO

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.


Assuntos
Antivirais/economia , Antivirais/uso terapêutico , Benzimidazóis/economia , Benzimidazóis/uso terapêutico , Análise Custo-Benefício , Fluorenos/economia , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Estudos de Coortes , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Sofosbuvir , Espanha , Resposta Viral Sustentada , Resultado do Tratamento , Uridina Monofosfato/economia , Uridina Monofosfato/uso terapêutico
11.
Rheumatol Int ; 36(2): 231-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26494567

RESUMO

Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038­84,076), €87,040 (78,496­95,584) and €102,683 (94,559­110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.


Assuntos
Adalimumab/economia , Adalimumab/uso terapêutico , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Custos de Medicamentos , Etanercepte/economia , Etanercepte/uso terapêutico , Infliximab/economia , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Redução de Custos , Análise Custo-Benefício , Etanercepte/efeitos adversos , Feminino , Humanos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Sistema de Registros , Indução de Remissão , Espanha , Fatores de Tempo , Resultado do Tratamento
12.
Neurologia ; 31(1): 9-17, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25288535

RESUMO

INTRODUCTION: The aim of this study was to analyse and compare procalcitonin (PCT) and C-reactive protein (CRP) as tools for detecting bacterial meningitis and predicting bacteraemia. METHODS: Prospective, observational, and descriptive analytical study of 98 consecutive patients aged ≥15 years and diagnosed with acute meningitis in an emergency department between August 2009 and July 2013. RESULTS: We analysed 98 patients with AM (66 males [67%]); mean age was 44±21 years. The diagnosis was bacterial meningitis in 38 patients (20 with bacteraemia); viral meningitis in 33; probable viral meningitis in 15; and presumptively diagnosed partially treated acute meningitis in 12. PCT had the highest area under the ROC curve (AUC) (0.996; 95% CI, 0.987-1; p<0.001). With a cutoff of ≥ 0.74 ng/ml, PCT achieved 94.7% sensitivity, 100% specificity, negative predictive value (NPV) of 93.9%, and positive predictive value (PPV) of 100%. The mean levels for PCT were11.47±7.76 ng/ml in bacterial meningitis vs. 0.10±0.15 ng/ml in viral meningitis (p <0.001). The AUC for CRP was 0.916 and a cutoff of ≥ 90 mg/L achieved 67.5% sensitivity, 86.3% specificity, PPV of 89.2%, and NPV of 90.4%. As a predictor of bacteraemia in bacterial meningitis, only PCT delivered a significant difference (14.7±7.1 ng/mL vs. 4.68±3.54 ng/mL, p<0.001). A cutoff of ≥ 1.1 ng/mL achieved 94.6% sensitivity, 72.4% specificity, NPV of 95.4%, and PPV of 69.2%; the AUC was 0.965 (95% CI, 0.921-1; p<0.001). CONCLUSIONS: PCT has a high diagnostic power for acute meningitis in emergency department patients. PCT outperforms CRP in the detection of bacterial aetiology and is a good predictor of bacteraemia in bacterial meningitis.


Assuntos
Calcitonina/sangue , Meningites Bacterianas/sangue , Adulto , Idoso , Proteína C-Reativa/análise , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Adulto Jovem
13.
Med Intensiva ; 40(3): 145-53, 2016 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26022940

RESUMO

OBJECTIVE: An evaluation is made of the hospital mortality predicting capacity of the main predictive scoring systems. DESIGN: A 2-year retrospective cohort study was carried out. SETTING: A third level ICU with surgical and medical patients. PATIENTS: All patients with multiorgan failure during the first day in the ICU. MAIN VARIABLES: APACHE II and IV, SAPS II and III, MPM II and hospital mortality. RESULTS: A total of 568 patients were included. Mortality rate: 39.8% (226 patients). Discrimination (area under the ROC curve; 95% CI): APACHE IV (0.805; 0.751-0.858), SAPS II (0.755; 0.697-0.814), MPM II (0.748; 0.688-0.809), SAPS III (0.737; 0.675-0.799) and APACHE II (0.699; 0.633-0.765). MPM II showed the best calibration, followed by SAPS III. APACHE II, SAPS II and APACHE IV showed very poor calibration. Standard mortality ratio (95% CI): APACHE IV 1.9 (1.78-2.02); APACHE II 1.1 (1.07-1.13); SAPS III 1.1 (1.06-1.14); SAPS II 1.03 (1.01-1.05); MPM 0.9 (0.86-0.94). CONCLUSIONS: APACHE IV showed the best discrimination, with poor calibration. MPM II showed good discrimination and the best calibration. SAPS II, in turn, showed the second best discrimination, with poor calibration. The APACHE II calibration and discrimination values currently disadvise its use. SAPS III showed good calibration with modest discrimination. Future studies at regional or national level and in certain critically ill populations are needed.


Assuntos
APACHE , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Humanos , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
14.
Med Intensiva ; 40(7): 395-402, 2016 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27068001

RESUMO

OBJECTIVES: To validate Trauma and Injury Severity Score (TRISS) methodology as an auditing tool in the Spanish ICU Trauma Registry (RETRAUCI). DESIGN: A prospective, multicenter registry evaluation was carried out. SETTING: Thirteen Spanish Intensive Care Units (ICUs). PATIENTS: Individuals with traumatic disease and available data admitted to the participating ICUs. INTERVENTIONS: Predicted mortality using TRISS methodology was compared with that observed in the pilot phase of the RETRAUCI from November 2012 to January 2015. Discrimination was evaluated using receiver operating characteristic (ROC) curves and the corresponding areas under the curves (AUCs) (95% CI), with calibration using the Hosmer-Lemeshow (HL) goodness-of-fit test. A value of p<0.05 was considered significant. MAIN VARIABLES OF INTEREST: Predicted and observed mortality. RESULTS: A total of 1405 patients were analyzed. The observed mortality rate was 18% (253 patients), while the predicted mortality rate was 16.9%. The area under the ROC curve was 0.889 (95% CI: 0.867-0.911). Patients with blunt trauma (n=1305) had an area under the ROC curve of 0.887 (95% CI: 0.864-0.910), and those with penetrating trauma (n=100) presented an area under the curve of 0.919 (95% CI: 0.859-0.979). In the global sample, the HL test yielded a value of 25.38 (p=0.001): 27.35 (p<0.0001) in blunt trauma and 5.91 (p=0.658) in penetrating trauma. TRISS methodology underestimated mortality in patients with low predicted mortality and overestimated mortality in patients with high predicted mortality. CONCLUSIONS: TRISS methodology in the evaluation of severe trauma in Spanish ICUs showed good discrimination, with inadequate calibration - particularly in blunt trauma.


Assuntos
Mortalidade Hospitalar , Índices de Gravidade do Trauma , Humanos , Unidades de Terapia Intensiva , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sistema de Registros , Espanha
15.
Med Intensiva ; 40(6): 327-47, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26440993

RESUMO

OBJECTIVE: To describe the characteristics and management of severe trauma disease in Spanish Intensive Care Units (ICUs). Registry of trauma in the ICU (RETRAUCI). Pilot phase. DESIGN: A prospective, multicenter registry. SETTING: Thirteen Spanish ICUs. PATIENTS: Patients with trauma disease admitted to the ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiology, out-of-hospital attention, registry of injuries, resources utilization, complications and outcome were evaluated. RESULTS: Patients, n=2242. Mean age 47.1±19.02 years. Males 79%. Blunt trauma 93.9%. Injury Severity Score 22.2±12.1, Revised Trauma Score 6.7±1.6. Non-intentional in 84.4% of the cases. The most common causes of trauma were traffic accidents followed by pedestrian and high-energy falls. Up to 12.4% were taking antiplatelet medication or anticoagulants. Almost 28% had a suspected or confirmed toxic influence in trauma. Up to 31.5% required an out-of-hospital artificial airway. The time from trauma to ICU admission was 4.7±5.3hours. At ICU admission, 68.5% were hemodynamically stable. Brain and chest injuries predominated. A large number of complications were documented. Mechanical ventilation was used in 69.5% of the patients (mean 8.2±9.9 days), of which 24.9% finally required a tracheostomy. The median duration of stay in the ICU and in hospital was 5 (range 3-13) and 9 (5-19) days, respectively. The ICU mortality rate was 12.3%, while the in-hospital mortality rate was 16.0%. CONCLUSIONS: The pilot phase of the RETRAUCI offers a first impression of the epidemiology and management of trauma disease in Spanish ICUs.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva , Ferimentos e Lesões/epidemiologia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Espanha
16.
Actas Dermosifiliogr ; 107(7): 577-90, 2016 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27316590

RESUMO

INTRODUCTION: While the introduction of biologics has improved the quality of life of patients with psoriasis and psoriatic arthritis, it may have increased the economic burden of these diseases. OBJECTIVE: To perform a systematic review of studies on the costs associated with managing and treating psoriasis and psoriatic arthritis in 5 European countries: Germany, Spain, France, Italy, and the United Kingdom. METHODS: We undertook a systematic review of the literature (up to May 2015) using the MEDLINE and EMBASE databases. The methodological quality of the studies identified was evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. We considered both direct costs (medical and nonmedical) and indirect costs, adjusted for country-specific inflation and converted to international dollars using purchasing power parity exchange rates for 2015 ($US PPP). RESULTS: The search retrieved 775 studies; 68.3% analyzed psoriasis and 31.7% analyzed psoriatic arthritis. The total annual cost per patient ranged from US $2,077 to US $13,132 PPP for psoriasis and from US $10,924 to US $17,050 PPP for psoriatic arthritis. Direct costs were the largest component of total expenditure in both diseases. The severity of these diseases was associated with higher costs. The introduction of biologics led to a 3-fold to 5-fold increase in direct costs, and consequently to an increase in total costs. CONCLUSIONS: We have analyzed the economic burden of psoriasis and psoriatic arthritis and shown that costs increase with the treatment and management of more severe disease and the use of biologics.


Assuntos
Efeitos Psicossociais da Doença , Psoríase/economia , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/economia , Artrite Psoriásica/terapia , França , Alemanha , Humanos , Itália , Psoríase/diagnóstico , Psoríase/terapia , Espanha , Reino Unido
17.
Haemophilia ; 21(3): 320-329, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25855214

RESUMO

OBJECTIVE: A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). METHODS: Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 µg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. RESULTS: Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. CONCLUSION: Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Análise Custo-Benefício , Fator VIIa/uso terapêutico , Hemofilia A/tratamento farmacológico , Pré-Medicação , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Fatores de Coagulação Sanguínea/administração & dosagem , Custos de Medicamentos , Fator VIII/imunologia , Fator VIIa/administração & dosagem , Custos de Cuidados de Saúde , Hemofilia A/complicações , Hemofilia A/diagnóstico , Hemofilia A/imunologia , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Isoanticorpos/imunologia , Modelos Estatísticos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Índice de Gravidade de Doença , Espanha
18.
Bioorg Med Chem Lett ; 25(22): 5115-20, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26475522

RESUMO

We report the optimization of a series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs) from an acyl dihydropyrazolo[1,5-a]pyrimidinone class. Investigation of exocyclic amide transpositions with this unique 5,6-bicyclic core were conducted in attempt to modulate physicochemical properties and identify a suitable backup candidate with a reduced half-life. A potent and selective PAM, 1-(2-(phenoxymethyl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-4(5H)-yl)ethanone (9a, VU0462807), was identified with superior solubility and efficacy in the acute amphetamine-induced hyperlocomotion (AHL) rat model with a minimum effective dose of 3mg/kg. Attempts to mitigate oxidative metabolism of the western phenoxy of 9a through extensive modification and profiling are described.


Assuntos
Encéfalo/metabolismo , Pirazóis/farmacocinética , Pirimidinas/farmacocinética , Pirimidinonas/farmacocinética , Receptor de Glutamato Metabotrópico 5/agonistas , Regulação Alostérica , Animais , Cães , Humanos , Ligantes , Masculino , Atividade Motora/efeitos dos fármacos , Pirazóis/sangue , Pirazóis/síntese química , Pirazóis/isolamento & purificação , Pirazóis/farmacologia , Pirimidinas/sangue , Pirimidinas/síntese química , Pirimidinas/farmacologia , Pirimidinonas/sangue , Pirimidinonas/síntese química , Pirimidinonas/isolamento & purificação , Pirimidinonas/farmacologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
19.
Int J Immunopathol Pharmacol ; 27(1): 53-67, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24674679

RESUMO

Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer therapy and are essential to immune responses, particularly through costimulation by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune intervention. PIK-75 is an efficient inhibitor of the PI3-K p110alpha catalytic subunits that suppresses tumor growth, and its effects on immune and autoimmune responses should be studied. Here, we describe the effect of PIK-75 on different immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in vitro (≥0.1 μM) inhibited T and B cell activation by Concanavalin A and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+ T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was prevented by caspase inhibitors. At low nanomolar concentrations (≤10 nM), PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-gamma production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts costimulated by ICOS, PIK-75 (less than 10 nM) inhibited IFN-gamma, IL-17A, or IL-21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG-specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE, modulating lymphocyte function and survival.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Hidrazonas/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Sulfonamidas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linfócitos T CD4-Positivos/enzimologia , Linfócitos T CD4-Positivos/patologia , Células Cultivadas , Citocinas/análise , Relação Dose-Resposta a Droga , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Hidrazonas/administração & dosagem , Hidrazonas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia
20.
Neurologia ; 29(3): 161-7, 2014 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-22795393

RESUMO

INTRODUCTION: The ability to drive after a stroke has been recognised by many authors as a sign of independence and it is closely associated with proper social reintegration. However, it remains unclear how the driving ability of an individual who has suffered a stroke should be evaluated, and by whom. Neurorehabilitation can produce improvements in patients who have suffered a stroke, and patients may therefore be able to resume driving at the end of an appropriate neurorehabilitation programme. The aim of this article is to present a literature review in order to highlight current evidence regarding methods for assessing driving ability and therapeutic methods applied in order to recover a patient's ability to drive. DEVELOPMENT: A literature search was performed in different databases for the period between 1993 and 2011. Studies were analysed individually based on methods for assessing driving ability and neurorehabilitation measures. CONCLUSIONS: If there are any doubts regarding stroke patients' ability to drive, patients should be assessed appropriately. The proper way to assess these patients according to the literature is by employing a multidisciplinary evaluation to determine who is able to take a road test. Neurorehabilitation exercises currently in use may be able to improve driving ability in stroke patients.


Assuntos
Condução de Veículo , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Humanos , Testes Neuropsicológicos
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