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We recently described C18 fatty acid acylated peptides as a new class of potent long-lasting single-chain RXFP1 agonists that displayed relaxin-like activities in vivo. Early pharmacokinetics and toxicological studies of these stearic acid acylated peptides revealed a relevant oxidative metabolism occurring in dog and minipig, and also seen at a lower extent in monkey and rat. Mass spectrometry combined to NMR spectroscopy studies revealed that the oxidation occurred, unexpectedly, on the stearic acid chain at ω-1, ω-2 and ω-3 positions. Structure-metabolism relationship studies on acylated analogues with different fatty acids lengths (C15-C20) showed that the extent of oxidation was higher with longer chains. The oxidized metabolites could be generated in vitro using liver microsomes and engineered bacterial CYPs. These systems were correlating poorly with in vivo metabolism observed across species; however, the results suggest that this biotransformation pathway might be catalyzed by some unknown CYP enzymes.
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Sistema Enzimático do Citocromo P-450 , Ácidos Graxos , Animais , Cães , Ratos , Sistema Enzimático do Citocromo P-450/metabolismo , Ácidos Graxos/metabolismo , Redes e Vias Metabólicas , Microssomos Hepáticos/metabolismo , Oxirredução , Ácidos Esteáricos , Suínos , Porco Miniatura/metabolismo , HaplorrinosRESUMO
Therapeutic interventions are being developed for Huntington's disease (HD), a hallmark of which is mutant huntingtin protein (mHTT) aggregates. Following the advancement to human testing of two [11C]-PET ligands for aggregated mHTT, attributes for further optimization were identified. We replaced the pyridazinone ring of CHDI-180 with a pyrimidine ring and minimized off-target binding using brain homogenate derived from Alzheimer's disease patients. The major in vivo metabolic pathway via aldehyde oxidase was blocked with a 2-methyl group on the pyrimidine ring. A strategically placed ring-nitrogen on the benzoxazole core ensured high free fraction in the brain without introducing efflux. Replacing a methoxy pendant with a fluoro-ethoxy group and introducing deuterium atoms suppressed oxidative defluorination and accumulation of [18F]-signal in bones. The resulting PET ligand, CHDI-650, shows a rapid brain uptake and washout profile in non-human primates and is now being advanced to human testing.
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Doença de Huntington , Tomografia por Emissão de Pósitrons , Animais , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Ligantes , Tomografia por Emissão de Pósitrons/métodos , Doença de Huntington/diagnóstico por imagem , Doença de Huntington/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismoRESUMO
Lipidation, a common strategy to improve half-life of therapeutic peptides, affects their tendency to oligomerize, their interaction with plasmatic proteins, and their catabolism. In this work, we have leveraged the use of NMR and SPR spectroscopy to elucidate oligomerization propensity and albumin interaction of different analogs of the two marketed lipidated GLP-1 agonists liraglutide and semaglutide. As most lipidated therapeutic peptides are administered by subcutaneous injection, we have also assessed in vitro their catabolism in the SC tissue using the LC-HRMS-based SCiMetPep assay. We observed that oligomerization had a shielding effect against catabolism. At the same time, binding to albumin may provide only limited protection from proteolysis due to the higher unbound peptide fraction present in the subcutaneous compartment with respect to the plasma. Finally, identification of catabolites in rat plasma after SC dosing of semaglutide showed a good correlation with the in vitro data, with Tyr19-Leu20 being the major cleavage site. Early characterization of the complex interplay between oligomerization, albumin binding, and catabolism at the injection site is essential for the synthesis of lipidated peptides with good pharmacokinetic profiles.
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Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Albuminas , Animais , Meia-Vida , Hipoglicemiantes , Liraglutida , Peptídeos , RatosRESUMO
The insulin-like peptide human relaxin-2 was identified as a hormone that, among other biological functions, mediates the hemodynamic changes occurring during pregnancy. Recombinant relaxin-2 (serelaxin) has shown beneficial effects in acute heart failure, but its full therapeutic potential has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. In this study, we report the development of long-acting potent single-chain relaxin peptide mimetics. Modifications in the B-chain of relaxin, such as the introduction of specific mutations and the trimming of the sequence to an optimal size, resulted in potent, structurally simplified peptide agonists of the relaxin receptor Relaxin Family Peptide Receptor 1 (RXFP1) (e.g., 54). Introduction of suitable spacers and fatty acids led to the identification of single-chain lipidated peptide agonists of RXFP1, with sub-nanomolar activity, high subcutaneous bioavailability, extended half-lives, and in vivo efficacy (e.g., 64).
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Lipopeptídeos/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Receptores de Peptídeos/agonistas , Relaxina/análogos & derivados , Relaxina/farmacologia , Sequência de Aminoácidos , Animais , Doenças Cardiovasculares , Linhagem Celular Tumoral , Células HEK293 , Meia-Vida , Humanos , Lipopeptídeos/genética , Lipopeptídeos/farmacocinética , Masculino , Simulação de Dinâmica Molecular , Estrutura Molecular , Mutação , Subunidades Proteicas , Ratos Sprague-Dawley , Relaxina/genética , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Pain is an important symptom in wound management, and the choice of treatment directly affects the patient's quality of life. Pain assessment (PA) is essential for quality wound care and, in Italy, mandatory by law. OBJECTIVE: To administer a dedicated learning survey to obtain a better sense of current PA practices, ensure more training, improve procedures, and reduce malpractice. METHODS: A 16-month learning survey of nurses based on a validated questionnaire developed for this project. RESULTS: The survey sample comprised 512 questionnaires. Of respondents, 78% were female, 56.1% were older than 40 years, 94% were RNs, and 6% were wound care specialist nurses. Participants performed a range of dressing changes per week (1-5, 46.3%; 6-20, 34.4%; >21, 19.3%). Although 93% of respondents considered PA important, only 26% recognized it as a vital parameter, and barely one-quarter (25.4%) were aware of current legislation mandating PA. The majority (95.3%) believed that PA is not consistent with pain perceived by the patient. Further, 87.3% stated that they did not have adequate knowledge to conduct a PA, 91.4% did not consider themselves up-to-date on PA, and 81% did not document PA results. However, specific wound care training leads to significantly better PA (P < .001): 71.9% of wound care specialist nurses recognized pain as a vital parameter, and 59.4% were aware of current legislation regarding PA; further, 81.3% consistently evaluated pain, 59.4% documented PA results, and 50% communicated the outcome to the physician in charge. CONCLUSIONS: The results illustrate the lack of sensitivity, training, and education that Italian RNs have regarding PA in wound care.
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Bandagens/estatística & dados numéricos , Manejo da Dor/enfermagem , Medição da Dor/enfermagem , Ferimentos e Lesões/enfermagem , Adulto , Feminino , Humanos , Itália , Masculino , Recursos Humanos de Enfermagem Hospitalar/normas , Qualidade de Vida , Cicatrização/fisiologiaRESUMO
The blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain and it has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to establish in vitro BBB models. Here, we describe the establishment of a human BBB model in a two-dimensional monolayer culture, derived from human induced pluripotent stem cells (hiPSCs). This model was characterized by a transendothelial electrical resistance (TEER) higher than 2000 Ωâcm2 and associated with negligible paracellular transport. The hiPSC-derived BBB model maintained the functionality of major endothelial transporter proteins and receptors. Some proprietary molecules from our central nervous system (CNS) programs were evaluated revealing comparable permeability in the human model and in the model from primary porcine brain endothelial cells (PBECs).
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Transporte Biológico/efeitos dos fármacos , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/metabolismo , Células Endoteliais/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Animais , Astrócitos/metabolismo , Transporte Biológico/fisiologia , Encéfalo/citologia , Diferenciação Celular/fisiologia , Células Cultivadas , Sistema Nervoso Central/química , Sistema Nervoso Central/metabolismo , Criopreservação/métodos , Humanos , Imuno-Histoquímica , Permeabilidade , SuínosRESUMO
The application of class I HDAC inhibitors as cancer therapies is well established, but more recently their development for nononcological indications has increased. We report here on the generation of improved class I selective human HDAC inhibitors based on an ethylketone zinc binding group (ZBG) in place of the hydroxamic acid that features the majority of HDAC inhibitors. We also describe a novel set of HDAC3 isoform selective inhibitors that show stronger potency and selectivity than the most commonly used HDAC3 selective tool compound RGFP966. These compounds are again based on an alternative ZBG with respect to the ortho-anilide that is featured in HDAC3 selective compounds reported to date.
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Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known pan-ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors. In particular, compound 2u is a brain penetrant ASIC2 inhibitor endowed with an optimal pharmacokinetic profile. This compound may represent a useful tool to validate in animal models in vivo the role of ASIC2 in different neurodegenerative central nervous system pathologies.
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INTRODUCTION: The error in medicine has long been discussed in scientific debates. The purpose of this study is to evaluate the degree knowledge, attitude and behavior of students in Nursing for the failure in the health sector. METHODS: It was administered to 231 students of Nursing of the Sapienza University of Rome (171 females and 60 males), aged between 21 and 45 years, a structured questionnaire in three questions that explore the experiences and opinions about the errors found in medical practice, the causes underlying them and the mistakes that should never be committed. Data were collected, stratified by sex, age, marital status, and analyzed using the χ2 test. Significance was set at p≤0.05. RESULTS: The 5 errors found more frequently in clinical practice by the students were the following: Errors that favors the onset of hospital infections (58.9%); Non adherence to protocols (50.2%); Patient care (45.9%); Errors due to the administration of therapies and drugs (45.9%); Errors relating to the execution of withdrawals (35.9%). The five cases considered most frequently responsible for such errors were: the rush (70.1%), followed by neglect / superficial (55%); disorganization (51.5%); not hygienically / infertility (50.6%) and inattention (42.9%). With regard to the errors that you should never commit, students have shown more frequently: the errors of administration of therapies / medications (69.3%); errors of prescription therapies / medications (58.9%); errors related to surgery (52.8%); the exchange of patient or misidentification of the patient (50.6%); errors that favor the occurrence of hospital infections (48.1%). CONCLUSIONS: The results of this study shows the importance of a culture of error in medicine, also as part of undergraduate education, in order to train and educate future health professionals to this issue in order to promoting patient safety and quality of health.
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Atitude Frente a Saúde , Erros Médicos , Estudantes de Enfermagem , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Roma , Adulto JovemRESUMO
The identification of a new series of P. falciparum growth inhibitors is described. Starting from a series of known human class I HDAC inhibitors a SAR exploration based on growth inhibitory activity in parasite and human cells-based assays led to the identification of compounds with submicromolar inhibition of P. falciparum growth (EC50 < 500 nM) and good selectivity over the activity of human HDAC in cells (up to >50-fold). Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies.
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This work describes a simple, sensitive and rapid liquid chromatography-high resolution mass spectrometry method for the quantitation of perhexiline and the simultaneous detection of perhexiline metabolites in C57bl/6 mice plasma. Only 5 µL of plasma was used for analysis. Pretreatment was limited to a 100-fold dilution ('dilute-and-shoot'). The analyte was detected by high resolution mass spectrometry (Orbitrap™ technology). Three scan events were performed over the entire chromatogram. Targeted single ion monitoring with data dependent acquisition was employed for perhexiline quantitation and confirmation, while full scan was used to perform untargeted detection of perhexiline phase I and phase II circulating metabolites. The calibration curve was linear (r(2)=0.990) ranging from 0.305 ng/mL (LLOQ) to 10000 ng/mL. Matrix effect was limited to 6.1%. The method was applied to a pharmacokinetic study of perhexiline in mouse plasma and the results obtained were compared to a standard sample preparation method based on protein precipitation and liquid chromatography-tandem mass spectrometry (MRM mode) detection. The new approach provided comparable results in terms of pharmacokinetics parameters estimate with a high sensitivity, additional information on perhexiline circulating metabolites and a low consumption of biological sample. The combination of the 'dilute-and-shoot' approach together with HRMS targeted and untargeted detection represents a suitable alternative to classic bioanalytical approaches in preclinical research.
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Perexilina/sangue , Perexilina/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Recent improvements in the identification of the genetic basis of long QT syndrome (LQTS) have led to significant changes in the diagnosis and management of this life-threatening condition. Genetic and electrocardiogram (ECG) tests are the most relevant examples among testing strategies for LQTS, yet their cost-effectiveness remains controversial. OBJECTIVE: The aim of this work was to review the available evidence on the cost-effectiveness of genetic and ECG testing strategies for the diagnosis of LQTS. METHODS: We performed a systematic review of the literature on the cost-effectiveness of genetic and ECG screening strategies for the early detection of LQTS using MEDLINE, EMBASE, and CRD databases between 2000 and 2013. A weighted version of Drummond checklist was instrumental in further assessing the quality of the included studies. RESULTS: We identified four eligible articles. Among them, genetic testing in the early detection of LQTS was cost-effective compared with no testing in symptomatic cases and not cost-effective when compared with watchful waiting in asymptomatic first-degree relatives of patients with established LQTS although it reached cost-effectiveness in higher risk subgroups, whereas ECG testing in neonates was highly cost-effective when compared with any screening strategy. CONCLUSIONS: LQTS profiling and patients' stratification have the potential to improve the disease management. Because of the limited current knowledge in this field, the present review recommends to perform further cost-effectiveness evaluations of the genetic and ECG screening alternatives, especially within European health care systems, which are still not available in the literature on genetic testing.
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Eletrocardiografia/economia , Testes Genéticos/economia , Custos de Cuidados de Saúde , Frequência Cardíaca , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/economia , Fatores Etários , Pesquisa Comparativa da Efetividade , Análise Custo-Benefício , Predisposição Genética para Doença , Frequência Cardíaca/genética , Humanos , Recém-Nascido , Síndrome do QT Longo/genética , Síndrome do QT Longo/fisiopatologia , Modelos Econômicos , Fenótipo , Valor Preditivo dos Testes , Adulto JovemRESUMO
OBJECTIVES: To develop a comparative, cost-effectiveness, and budget impact analysis of Therakos online extracorporeal photopheresis (ECP) compared with the main alternatives used for the treatment of steroid-refractory/resistant chronic graft-versus-host disease (cGvHD) in Italy. METHODS: The current therapeutic pathway was identified by searching medical databases and from the results of a survey of practice in Italian clinical reference centers. A systematic review was performed to evaluate the efficacy and safety of second-line alternatives. Budget impact and cost-effectiveness analyses were performed from the Italian National Health Service perspective over a 7-year time horizon through the adaption of a Markov model. The following health states were considered: complete and partial response, stable disease, and progression. A discount rate of 3% was applied to costs and outcomes. RESULTS: The most common alternatives used in Italy for the management of steroid-refractory/resistant cGvHD were ECP, mycophenolate, pentostatin, and imatinib. The literature review highlighted that complete and partial responses are higher with ECP than with the alternatives while serious adverse events are less common. The economic analysis showed that Therakos online ECP represents the dominating alternative, in that it delivers greater benefit at a lower cost. In fact, according to the alternatives considered, cost saving ranged from 3237.09 to 19,903.51 per patient with 0.04 to 0.21 quality-adjusted life-year gained. CONCLUSIONS: Therakos online ECP should be considered an effective, safe, and cost-effective alternative in steroid-refractory/resistant cGvHD. There is inequality in access, and a dedicated reimbursement tariff, however, should be introduced to overcome these barriers.
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Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/terapia , Fotoferese/métodos , Avaliação da Tecnologia Biomédica/métodos , Doença Crônica , Análise Custo-Benefício/métodos , Análise Custo-Benefício/normas , Feminino , Doença Enxerto-Hospedeiro/economia , Humanos , Itália/epidemiologia , Masculino , Fotoferese/economia , Fotoferese/normas , Avaliação da Tecnologia Biomédica/normas , Resultado do TratamentoRESUMO
OBJECTIVES: Haemophilia A is a congenital disorder of coagulation that mainly affects males and causes a considerable use of resources, especially when hemophilic patients are treated with prophylaxis. The aim of the present review was to discuss and appraise the methodological aspects and results of published economic evaluations of haemophilia A treatments in the last decade. METHODS: The literature search, performed by consulting four engines, covered studies published between 2002 and 2014. Full economic evaluations published in English language were identified and included in the review. A quality assessment of the studies was also carried out based on Drummond's checklist. RESULTS: After careful evaluations of the identified records, 5 studies were reviewed. Primary and secondary prophylaxis resulted cost-effective compared to on-demand therapy: the ICER of primary prophylaxis ranged from 40.236 to 59.315/QALY gained, while the ICER of secondary prophylaxis was 40.229/QALY gained. Furthermore, 60% were high quality and 40% were medium quality studies. CONCLUSIONS: The review underlines the cost-effectiveness of prophylaxis versus on-demand treatment and the different methodological approaches applied. Further economic evaluations are required with models that reflect the clinical reality and consumption of resources in each country.
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Hemofilia A/economia , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Custos de Medicamentos , Fator VIII/economia , Fator VIII/uso terapêutico , Custos de Cuidados de Saúde , Hemofilia A/tratamento farmacológico , Hemofilia A/prevenção & controle , Humanos , MasculinoRESUMO
Neuroactive metabolites in the kynurenine pathway of tryptophan catabolism are associated with neurodegenerative disorders. Tryptophan is transported across the blood-brain barrier and converted via the kynurenine pathway to N-formyl-L-kynurenine, which is further degraded to L-kynurenine. This metabolite can then generate a group of metabolites called kynurenines, most of which have neuroactive properties. The association of tryptophan catabolic pathway alterations with various central nervous system (CNS) pathologies has raised interest in analytical methods to accurately quantify kynurenines in body fluids. We here describe a rapid and sensitive reverse-phase HPLC-MS/MS method to quantify L-kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxy-L-kynurenine (3HK) and anthranilic acid (AA) in rat plasma. Our goal was to quantify these metabolites in a single run; given their different physico-chemical properties, major efforts were devoted to develop a chromatography suitable for all metabolites that involves plasma protein precipitation with acetonitrile followed by chromatographic separation by C18 RP chromatography, detected by electrospray mass spectrometry. Quantitation range was 0.098-100 ng/ml for 3HK, 9.8-20,000 ng/ml for KYN, 0.49-1000 ng/ml for KYNA and AA. The method was linear (r>0.9963) and validation parameters were within acceptance range (calibration standards and QC accuracy within ±30%).
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Barreira Hematoencefálica/metabolismo , Cinurenina/química , Cinurenina/metabolismo , Plasma/química , Animais , Cromatografia Líquida de Alta Pressão , Ácido Cinurênico/sangue , Ácido Cinurênico/química , Cinurenina/sangue , Ratos , Triptofano/sangue , Triptofano/química , ortoaminobenzoatos/sangue , ortoaminobenzoatos/químicaRESUMO
BACKGROUND: Obesity represents an important public health issue. An assessment of its costs would be useful to provide recommendations for policy and decision-making strategies. The aims of our study were to carry out a systematic review to assess the economic burden of adult obesity in terms of direct and indirect costs and to perform a quality appraisal of the analysed studies. METHODS: A literature search was carried out on PubMed, Scopus and Cochrane Library to retrieve cost-of-illness (COI) analyses focused on adult (aged 18 years or more) overweight or obese people and published up to 2013. COI analyses that considered direct and indirect costs were included. Each included manuscript was independently appraised by three groups of researchers on the basis of the British Medical Journal Drummond's checklist. RESULTS: Approximately 2044 articles were initially retrieved, and 17 were included in the current review. The included studies showed a medium-high-quality level. The available studies seemed to be heterogeneous both in terms of methodology and results reporting. However, as many studies have been conducted from the payer perspective, just direct medical costs can be considered exhaustive. As only three studies included considered also indirect costs, there is no strong evidence to give a comprehensive picture of this phenomenon also from the societal perspective. CONCLUSION: The review confirmed that obesity absorbs a huge amount of health-care resources. Further research is therefore needed to better understand the economic impact and to identify and promote public health strategies to tackle obesity.
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Atenção à Saúde/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Obesidade/economia , Adulto , Efeitos Psicossociais da Doença , Análise Custo-Benefício , HumanosRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. METHODS: SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. RESULTS: Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2-5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of 32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. CONCLUSIONS: The assessment supports the use of belimumab into the SLE treatment paradigm in Italy.
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Anticorpos Monoclonais Humanizados , Imunossupressores , Lúpus Eritematoso Sistêmico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Análise Custo-Benefício , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/economia , Imunossupressores/uso terapêutico , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/economia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Qualidade de VidaRESUMO
OBJECTIVE: The Health Technology Assessment (HTA) approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women. METHOD: Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation. RESULTS: In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance. CONCLUSION: Denosumab could add value in the prevention of osteoporotic fractures.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Pós-Menopausa , Avaliação da Tecnologia Biomédica , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/economia , Conservadores da Densidade Óssea/economia , Orçamentos , Análise Custo-Benefício , Denosumab , Feminino , Hospitalização/economia , Humanos , Itália/epidemiologia , Cadeias de Markov , Pessoa de Meia-Idade , Fraturas por Osteoporose/economia , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa/efeitos dos fármacos , Avaliação da Tecnologia Biomédica/economia , Avaliação da Tecnologia Biomédica/ética , Avaliação da Tecnologia Biomédica/organização & administração , Resultado do TratamentoRESUMO
Public Health (PH) and Primary Health Care (PHC) need to be better integrated, at different levels of the healthcare system, in order to improve health and social outcomes. The aim of this study was to review international models and approaches supporting the integration of PH and PHC and to classify these according to their main focus. A literature search was performed using the main scientific databases, to identify national and international journal publications regarding models to support integration between PH and PHC. The final set of the documents provided a broad coverage of the topic. Four models of integration were identified: general integration, chronic disease prevention, targeted prevention or care delivery and infection control. Models differed in their levels of implementation, stages of development and focus. This review, by classifying the main characteristics and results of the experiences retrieved, indicates a relatively scarce use of integration models in the global health care landscape, with the exception of Canada. In fact, Canada has been a leader in developing models of integrated health systems that combine tailored approaches to influence personal health behaviour and community-oriented approaches to influence the health of the population. The review also revealed a general lack of experience in evaluating the sustainability of integration between PH and PHC, not only in terms of cost-effectiveness, but also in terms of better health and work conditions and self-perceived quality of care in the population. Collaboration between PH and PHC seems to be an important strategy for achieving principles of equity and access in health care and for ensuring a more equal distribution of health care services.
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Comportamento Cooperativo , Atenção Primária à Saúde , Saúde Pública , Doença Crônica/prevenção & controle , Prestação Integrada de Cuidados de Saúde , Países Desenvolvidos , Países em Desenvolvimento , Saúde Global , Humanos , Controle de Infecções , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Influenza epidemics are responsible for high mortality and morbidity rates in particular among elderly and high risk groups. This review is aimed at assessing the economic value of vaccination in these groups. A search of full economic evaluations of influenza vaccination in comparison with no interventions was performed on PubMed from January 1990 to May 2011. Only economic evaluations dealing with elderly and high risk groups were considered. The quality of selected articles was assessed through Drummond's checklist. Sixteen cost-effectiveness analyses and four cost-benefit analyses were included: overall, the quality of studies was fairly good. The vaccination was demonstrated to be cost-effective or cost-saving in almost all studies, independently by the perspective and the type of analysis. Influenza vaccination is a worthwhile intervention from the pharmacoeconomic view-point, anyway a standardization of methods should be desirable in order to guarantee the comparability and transferability of results.