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2.
Arq. ciências saúde UNIPAR ; 27(5): 2161-2174, 2023.
Artigo em Português | LILACS | ID: biblio-1433772

RESUMO

A implementação das PICs no Brasil é uma realidade, dessa forma, compreende-se que o enfermeiro é o profissional que em tese deve possuir habilidades para aplicar as técnicas em pacientes. Com base nisso, o objetivo do trabalho foi descrever a atuação da enfermagem através de Planos de ações por intermédio das PICs em individuos com diminuição da qualidade de vida em razão do desenvolvimento de doenças crônicas degenerativas. Dessa forma, o presente artigo trata-se de uma revisão integrativa de literatura. Os resultados obtidos mostram que a aplicabilidade das PICs, está consolidada, sendo uma prática bastante utilizada na intervenção terapêutica de indivíduos portadores de doenças crônicas degenerativas, na qual as mais utilizadas são: plantas medicinais, reiki, homeopatia, acupuntura e auricuoterapia, entretanto, em relação a assistência de enfermagem, foi observado impasses em relação a capacitação profissional. Logo, concluímos que com base nas produções cientificas existentes a respeito das PICs, a prática infere em diversos benefícios ao indivíduo, estas que se convergem a promoção de maior qualidade de vida ao paciente com doenças crônicas, porém, a falta de capacitação profissional revela um impasse ainda persistente.


The implementation of PICs in Brazil is a reality, therefore, it is understood that the nurse is the professional who, in theory, must have the skills to apply the techniques to patients. Based on this, the objective of the study was to describe the role of nursing through Action Plans through PICs in individuals with reduced quality of life due to the development of chronic degenerative diseases. Thus, this article is an integrative literature review. The results obtained show that the applicability of PICs is consolidated, being a practice widely used in the therapeutic intervention of individuals with chronic degenerative diseases, in which the most used are: medicinal plants, reiki, homeopathy, acupuncture and auricutherapy, however, in regarding nursing care, impasses regarding professional training were observed. Therefore, we conclude that based on the existing scientific productions regarding PICs, the practice infers in several benefits to the individual, these that converge to the promotion of a better quality of life for the patient with chronic diseases, however, the lack of professional training reveals a stalemate still persistent.


La implementación de los PICs en Brasil es una realidad, por lo tanto, se entiende que la enfermera es el profesional que, en teoría, debe tener las habilidades para aplicar las técnicas a los pacientes. Con base en esto, el objetivo del estudio fue describir el papel de la enfermería a través de Planes de Acción por medio de PICs en individuos con calidad de vida reducida debido al desarrollo de enfermedades crónico degenerativas. Así, este artículo es una revisión bibliográfica integradora. Los resultados obtenidos muestran que la aplicabilidad de los PICs está consolidada, siendo una práctica ampliamente utilizada en la intervención terapéutica de individuos con enfermedades crónicas degenerativas, en la que las más utilizadas son: plantas medicinales, reiki, homeopatía, acupuntura y auricuterapia, sin embargo, en lo que respecta a los cuidados de enfermería, se observaron impasses en cuanto a la formación profesional. Por lo tanto, concluimos que con base en las producciones científicas existentes en relación a las PICs, la práctica infiere en varios beneficios al individuo, estos que convergen a la promoción de una mejor calidad de vida para el paciente con enfermedades crónicas, sin embargo, la falta de formación profesional revela un impasse aún persistente.


Assuntos
Terapias Complementares/enfermagem , Doença Crônica/enfermagem , Doença Crônica/tratamento farmacológico , Qualidade de Vida , Terapias Complementares/instrumentação , Terapias Complementares/métodos , Revisão , Capacitação Profissional , Enfermeiras e Enfermeiros , Cuidados de Enfermagem
3.
Arq. ciências saúde UNIPAR ; 26(3): 643-656, set-dez. 2022.
Artigo em Português | LILACS | ID: biblio-1399314

RESUMO

O Diabetes Mellitus (DM) é uma doença crônica, que tem elevada prevalência na sociedade e representa um problema de saúde pública devido à natureza de suas complicações, acredita-se que a dificuldade na manutenção do tratamento, pode estar relacionada a deficiência ou falta de adesão. O estudo teve como objetivo relatar à adesão ao tratamento do Diabetes Mellitus na Atenção Primária a Saúde. Trata-se de um estudo descritivo, com abordagem qualitativa, realizado com 30 pacientes diabéticos de uma Unidade de Atenção Primária à Saúde de Guaiúba-CE, no período de agosto a outubro de 2021. A coleta de dados deu-se por entrevista semiestruturada utilizando questões norteadoras sobre adesão ao tratamento, adoção de práticas promotoras de saúde e posteriormente sujeita a análise de conteúdo. Observou-se que a adesão ao tratamento do diabetes envolve inúmeros desafios, relacionados principalmente ao usuário e sistemas de saúde/profissionais. Os maiores desafios encontrados foram em relação a supervalorização do tratamento medicamentoso frente a adoção de hábitos saudáveis e de ações promotoras de autocuidado. Nesse cenário, nota-se a importância de conhecer os fatores que influenciam na adesão ao tratamento com o intuito de se lançar estratégias para aperfeiçoar o planejamento de ações e intervenções a esses pacientes.


Diabetes Mellitus (DM) is a chronic disease that is highly prevalent in society and represents a public health problem due to the nature of its complications. The study aimed to report on the adherence to treatment of Diabetes Mellitus in Primary Health Care. This is a descriptive study, with a qualitative approach, conducted with 30 diabetic patients from a Primary Health Care Unit in Guaiúba-CE, in the period from August to October 2021. Data were collected through semi-structured interviews using guiding questions about adherence to treatment, adoption of health-promoting practices and later subjected to content analysis. It was observed that diabetes treatment adherence involves numerous challenges, mainly related to the user and health systems/professionals. The biggest challenges found were related to the overvaluation of drug treatment against the adoption of healthy habits and self-care promoting actions. In this scenario, it is important to know the factors that influence treatment adherence in order to develop strategies to improve the planning of actions and interventions for these patients.


La diabetes mellitus (DM) es una enfermedad crónica, que tiene una alta prevalencia en la sociedad y representa un problema de salud pública debido a la naturaleza de sus complicaciones, se cree que la dificultad para mantener el tratamiento puede estar relacionada con la deficiencia o falta de adherencia. El estudio tenía como objetivo informar sobre la adherencia al tratamiento de la Diabetes Mellitus en Atención Primaria. Se trata de un estudio descriptivo con enfoque cualitativo, realizado con 30 pacientes diabéticos de una Unidad de Atención Primaria de Salud de Guaiúba-CE, en el período de agosto a octubre de 2021. La recogida de datos se llevó a cabo mediante entrevistas semiestructuradas en las que se utilizaron preguntas orientativas sobre la adherencia al tratamiento y la adopción de prácticas de promoción de la salud, y posteriormente se sometieron a un análisis de contenido. Se ha observado que el acceso al tratamiento de la diabetes conlleva numerosos desafíos, relacionados principalmente con el usuario y los sistemas de salud/profesionales. Los mayores retos encontrados estaban relacionados con la sobrevaloración del tratamiento farmacológico frente a la adopción de hábitos saludables y acciones de promoción del autocuidado. En este escenario, se constata la importancia de conocer los factores que influyen en la adherencia al tratamiento para poner en marcha estrategias que mejoren la planificación de las acciones e intervenciones para estos pacientes.


Assuntos
Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pacientes , Atenção Primária à Saúde/organização & administração , Diabetes Mellitus/tratamento farmacológico , Cooperação e Adesão ao Tratamento , Autocuidado/instrumentação , Sistema Único de Saúde , Preparações Farmacêuticas/análise , Exercício Físico/fisiologia , Saúde Pública , Doença Crônica/tratamento farmacológico , Diabetes Mellitus/diagnóstico , Tratamento Farmacológico , Dieta Saudável , Promoção da Saúde , Acesso aos Serviços de Saúde , Cuidados de Enfermagem/métodos
4.
Québec; INESSS; mai 2022.
Não convencional em Francês | BRISA/RedTESA | ID: biblio-1516366

RESUMO

INTRODUCTION: Au cours des dernières années, les médicaments biologiques se sont ajoutés à l'arsenal thérapeutique des maladies inflammatoires chroniques. Afin d'assurer un usage responsable de ces agents coûteux, leur paiement est actuellement autorisé suivant l'essai préalable de certains traitements conventionnels, notamment des immunosuppresseurs, à moins d'intolérances ou de contre-indications. Toutefois, des associations médicales en gastroentérologie et en dermatologie font état d'un décalage entre les indications de paiement des médicaments biologiques et les meilleures pratiques cliniques. Actuellement, lorsque l'utilisation des médicaments biologiques sans l'essai préalable des immunosuppresseurs est requise, une assistance par un programme de soutien aux patients et aux patientes pourrait être offerte par les fabricants des médicaments biologiques, selon certaines conditions. Dans le traitement des maladies inflammatoires de l'intestin, l'utilisation précoce des médicaments biologiques par le biais de ces programmes de soutien semble être une pratique bien établie et largement répandue depuis plusieurs années. Avec l'entrée en vigueur en avril 2021 de l'article 80.2 de la Loi sur l'assurance médicaments, lequel interdit le paiement ou le remboursement d'un médicament ou d'une fourniture dont le paiement est couvert par le régime général d'assurance médicaments, des associations médicales ont partagé des préoccupations quant à l'accès des médicaments biologiques sans l'essai préalable des immunosuppresseurs au ministère de la Santé et des Services Sociaux (MSSS). Notons que les médicaments biologiques, qu'ils soient de référence ou biosimilaires, font actuellement partie des exceptions prévues au règlement. Afin d'évaluer la pertinence des préalables de traitement dans les indications de paiement des médicaments biologiques, le MSSS a demandé à l'Institut national d'excellence en santé et en services sociaux (INESSS) de mobiliser les savoirs quant à la place des immunosuppresseurs et des médicaments biologiques dans les domaines de la gastroentérologie et de la dermatologie. MÉTHODOLOGIE: Tout d'abord, les indications de paiement des médicaments biologiques inscrits sur les listes de médicaments du Québec (ou dont la décision du ministre est en attente) ont été comparées à celles des autres provinces canadiennes. Ensuite, une revue rapide de la littérature a été réalisée pour répertorier notamment les recommandations des guides de pratique clinique (GPC) concernant la place des médicaments biologiques et des immunosuppresseurs dans la prise en charge de la maladie de Crohn chez l'adulte et l'enfant, de la colite ulcéreuse chez l'adulte et du psoriasis en plaques chez l'adulte. Finalement, les savoirs expérientiels et contextuels ont été recueillis par l'intermédiaire d'une invitation à recevoir des commentaires sur le plan de travail de l'INESSS et d'une consultation d'experts comprenant des gastroentérologues et des dermatologues. RÉSULTATS: Les GPC retenus dans les travaux relatent le manque d'étude de bonne qualité évaluant le moment optimal pour l'introduction des médicaments biologiques dans le traitement. Néanmoins, selon les données disponibles et le degré de valorisation de plusieurs autres facteurs, y compris les risques de complications, la gravité de la maladie, la réponse aux traitements antérieurs et les coûts, les sociétés savantes ont émis des recommandations concernant diverses séquences de traitement avec les médicaments biologiques, autant avant que suivant un traitement par les immunosuppresseurs. Pour le traitement des maladies inflammatoires de l'intestin, la plupart des GPC sélectionnés présentent des recommandations au sujet de l'utilisation des médicaments biologiques suivant un traitement conventionnel, lequel inclut l'acide 5-aminosalicylique (5-ASA) et (ou) les corticostéroïdes et (ou) les immunosuppresseurs. Plusieurs GPC font toutefois également état d'un changement de paradigme vers l'utilisation des médicaments biologiques en première intention de traitement, particulièrement chez les personnes qui ont des facteurs de risque de mauvais pronostic, afin de prévenir les complications, l'hospitalisation et le recours à la chirurgie. Très peu d'essais ont comparé l'efficacité des médicaments biologiques par rapport à celle des immunosuppresseurs, et ceux répertoriés ne sont pas représentatifs de la pratique clinique actuelle avec les médicaments biologiques. Les immunosuppresseurs sont généralement recommandés pour le maintien de la rémission et pourraient constituer une option de traitement acceptable suivant l'atteinte d'une rémission par les corticostéroïdes, mais leur utilisation suscite des préoccupations liées à leur innocuité, notamment le risque de lymphome T hépatosplénique associé aux thiopurines, telles l'azathioprine et la mercaptopurine. Pour le traitement du psoriasis en plaques, les recommandations issues des GPC sélectionnés concernant la place des médicaments biologiques dans le traitement sont peu nombreuses. Néanmoins, tous les GPC retenus s'accordent pour recommander l'utilisation des médicaments biologiques suivant un traitement par les agents de rémission systémiques conventionnels, lesquels incluent les immunosuppresseurs (principalement la cyclosporine et le méthotrexate) et l'acitrétine. Un GPC suggère également l'introduction précoce des médicaments biologiques dans des situations particulières. L'efficacité différentielle entre les médicaments biologiques et les agents de rémission systémiques conventionnels relève principalement de comparaisons indirectes. Une méta-analyse en réseau réalisée par le groupe Cochrane rapporte que la plupart des médicaments biologiques serait plus efficace que les agents de rémission systémiques conventionnels pour atteindre une réduction d'au moins 90 % sur le Psoriasis Area and Severity Index (PASI90). Par ailleurs, des enjeux d'innocuité sont liés aux agents de rémission systémiques conventionnels : le traitement continu par la cyclosporine n'est pas recommandé en pratique au-delà d'un an en raison des risques de néphrotoxicité, l'acitrétine pouvant causer des effets muco-cutanés et le méthotrexate, entraîner une hépatotoxicité. PERSPECTIVE DES EXPERTS ET AUTRES PARTIES PRENANTES: Pour le traitement des maladies inflammatoires de l'intestin, malgré l'absence de données de bonne qualité entre les immunosuppresseurs et les médicaments biologiques, les experts consultés estiment, selon leur expérience clinique, que les médicaments biologiques présentent une efficacité supérieure et un profil d'innocuité favorable par rapport aux immunosuppresseurs. Dans ce contexte, ils considèrent que l'essai des immunosuppresseurs avant l'autorisation des médicaments biologiques expose les patients à des risques de toxicité, de progression de la maladie et de complications. Afin d'éviter ces risques aux personnes qui en font usage, les cliniciens rapportent que l'utilisation des médicaments biologiques sans l'essai préalable des immunosuppresseurs par l'intermédiaire des programmes de soutien aux patients financés par les fabricants est une pratique bien établie au Québec depuis plusieurs années. En dermatologie, les cliniciens rapportent que les préalables de traitement dans les indications de paiement des médicaments biologiques pour le traitement du psoriasis en plaques pourraient forcer le choix d'options thérapeutiques souvent inappropriées pour les patients. Ils mentionnent que seul le méthotrexate dispose d'une réelle place dans le traitement du psoriasis en plaques modéré à grave. Les cliniciens reconnaissent que les délais engendrés par l'essai préalable d'au moins deux agents de rémission systémiques conventionnels, tel que requis actuellement dans les indications de paiement des médicaments biologiques, n'influencent pas le pronostic vital des patients. Toutefois, ils jugent important d'adapter le traitement à la condition particulière des personnes qui en font usage afin de réduire les plaques de psoriasis tout en limitant la survenue d'effets indésirables. CONCLUSIONS: Le moment optimal pour l'introduction des médicaments biologiques par rapport aux immunosuppresseurs dans les domaines de la gastroentérologie et de la dermatologie n'a pas été évalué dans des études de bonne qualité. Ainsi, les présents travaux démontrent une inadéquation entre la pratique clinique actuelle en gastroentérologie et les données probantes de bonne qualité disponibles. À ce propos, l'expérience clinique acquise au cours des dernières années avec les médicaments biologiques dans le traitement des maladies inflammatoires de l'intestin a mené les gastroentérologues à préconiser leur utilisation sans l'essai préalable des immunosuppresseurs. Les cliniciens estiment que l'exigence d'un traitement antérieur par les immunosuppresseurs dans les indications de paiement des médicaments biologiques pour le traitement des maladies inflammatoires de l'intestin devrait être retirée, principalement puisque les immunosuppresseurs retarderaient la guérison et exposeraient les patients à des risques de toxicité et de complications non négligeables, selon eux. Bien que la situation soit quelque peu différente en dermatologie, les cliniciens consultés soutiennent également le retrait de cette exigence pour le psoriasis en plaques.


INTRODUCTION: Over the past few years, biologic agents have been included in the therapeutic arsenal for treating chronic inflammatory diseases. To ensure responsible use of these costly drugs, their payment is currently only authorized following the use of conventional treatments (notably immunosuppressants), except in the presence of intolerances or contraindications. However, medical associations in gastroenterology and dermatology report a disconnect between coverage information for biologic agents and best clinical practices. At present, when biologic agents must be used without any prior trials of immunosuppressants, patients can, under certain conditions, receive assistance from biologic drug manufacturers for access through a patient support program. In the treatment of inflammatory bowel diseases, the early use of biologic agents through such support programs appears to be an established and widespread practice for several years. With the coming into force of section 80.2 of the Act respecting prescription drug insurance in April 2021, which prohibits the payment or reimbursement of a medication or supply covered by the Public Prescription Drug Insurance Plan, medical associations shared their concerns regarding access to biologic agents without any prior trials of immunosuppressants with the Ministère de la Santé et des Services sociaux (department of health issues and social services) (MSSS). It bears noting that biologic agents, whether they are reference products or biosimilars, are included in the exceptions provided for under the regulation. To assess the relevance of the prerequisite of the use of an immunosuppressant for the coverage of biologic agents, the MSSS asked the Institut national d'excellence en santé et en services sociaux (INESSS) to draw on the existing knowledge regarding the role of immunosuppressants and biologic agents in gastroenterology and dermatology. METHODOLOGY: First, coverage information for biologic agents listed on Québec drug formulary (or for which the Minister's decision is pending) was compared with that in other Canadian provinces. Then, a rapid review of the literature was performed to identify CPG (Clinical practice guidelines) recommendations regarding the place of biologic agents and immunosuppressants in the treatment algorithm of Crohn's disease in adults and children, ulcerative colitis in adults and plaque psoriasis in adults. Lastly, experiencebased and contextual knowledge was gathered through an invitation to receive feedback on the INESSS' work plan and from a consultation panel including gastroenterologists and dermatologists. RESULTS: The CPGs selected report a lack of quality studies on the best timing for incorporating biologic agents into a treatment plan. However, according to available data and the importance of several other factors, including the risk of complications, the severity of the illness, the response to previous treatments and the associated costs, learned societies made recommendations regarding various sequences of treatment with biologic agents, both before and after a treatment with immunosuppressants. For the treatment of inflammatory bowel diseases, most of the CPGs selected comprise recommendations as to the use of biologic agents following a conventional treatment that includes 5-ASA (aminosalicylic acids) and/or corticosteroids and/or immunosuppressants. Numerous CPGs, however, report a paradigm shift towards the use of biologic drugs as the front-line treatment, especially for persons at risk of a poor prognosis, to prevent complications, hospitalization and the need for surgery. Very few clinical trials have compared the efficacy of biologic agents and immunosuppressants, and the ones reported are not representative of current clinical practices with biologic agents. Immunosuppressants are generally recommended to maintain complete remission and could prove an acceptable treatment option once remission is achieved with corticosteroids; however, concerns associated with their safety have been raised, notably regarding the risk of hepatosplenic T-cell lymphoma due to thiopurines, such as azathioprine and mercatopurine. There are few recommendations in the selected CPGs regarding the role of biologic drugs in the treatment of plaque psoriasis. However, all of the CPGs selected agree in recommending the use of biologic drugs following a treatment with conventional systemic agents, which include immunosuppressants (primarily cyclosporine and methotrexate) and acitretin. One CPG also suggests resorting to the early use of biologic agents in special situations. The differential efficacy of biologic drugs and conventional systemic agents was mainly established through indirect comparisons. A network meta-analysis performed by Cochrane reports that most biologic drugs would be more effective than conventional systemic agents at achieving a decrease of at least 90% on the Psoriasis Area and Severity Index (PASI90). In addition, conventional systemic agents have certain safety issues: ongoing treatment with cyclosporine is not recommended beyond one year given the risks of nephrotoxicity, acitretin can cause mucocutaneous effects and methotrexate can induce hepatotoxicity. OPINIONS OF EXPERTS AND OTHER STAKEHOLDERS: For the treatment of inflammatory bowel diseases, despite the lack of quality data on immunosuppressants and biologic agents, the experts consulted believe, based on their clinical experience, that biologic agents offer a superior efficacy and a more favourable safety profile compared to immunosuppressants. Given this, they also consider that requiring a trial with an immunosuppressant before allowing the use of a biologic agent exposes patients to risks, among them toxicity, disease progression and complications. To avoid such risks, clinicians report that the use of biologic agents without the prior use of immunosuppressants through manufacturer-funded patient support programs is a wellestablished practice in Québec since many years. Clinicians in the field of dermatology report that the inclusion of preliminary treatments for the coverage of biologic agents in plaque psoriasis could result in patients being inappropriately treated. They mention that among the systemic drugs listed as prerequisite (acitretin, cyclosporin and methotrexate), methotrexate is the preferred agent for treating moderate to severe plaque psoriasis. The clinicians acknowledge that the delays resulting from the trial of at least two traditional systemic agents, as currently required in the coverage information for biologic agents, is not life-threatening for patients. However, they do believe that the treatment should be tailored based on the specific condition of the persons who benefit from it, to reduce psoriatic plaques while limiting the occurrence of adverse effects. CONCLUSIONS: The optimal timing for the introduction of biologics agents versus immunosuppressants in the field of gastroenterology and dermatology has not been assessed in good quality studies. Current research illustrates a discrepancy between actual clinical practices in gastroenterology and the quality evidence-based data available. The clinical experience using biologic drugs to treat inflammatory bowel diseases acquired over the past few years has led gastroenterologists to favour their use without a preliminary treatment with immunosuppressants. Clinicians consider that requiring such a prior treatment with immunosuppressants in the payment indications of biologic drugs for inflammatory bowel diseases should be ceased, mainly because immunosuppressants delay healing and expose patients to risks that include toxicity and non-negligeable complications. And while the circumstances are somewhat different in the field of dermatology, the clinicians consulted also support the removal of this requirement from payment indications of biologic drugs in the case of plaque psoriasis. Given a lack of data, this work did not evaluate the economic impact of withdrawing the requirement regarding prior treatment with immunosuppressants from the coverage information for biologic agents. This would likely generate a significant increase in costs, but the amounts involved should be compared to the cost of complications and other avoidable consequences. It should also be noted that a large portion of these costs are currently borne by the manufacturers, through patient support programs.


Assuntos
Humanos , Fatores Biológicos/uso terapêutico , Doença Crônica/economia , Doença Crônica/tratamento farmacológico , Imunossupressores/uso terapêutico , Avaliação em Saúde/economia , Eficácia
5.
Int J Mol Sci ; 23(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35269545

RESUMO

For decades, scientists have been doing a lot of research and exploration to find effective long-term analgesic and/or disease-modifying treatments. Microneedles (MNs) are a simple, effective, and painless transdermal drug delivery technology that has emerged in recent years, and exhibits great promise for realizing intelligent drug delivery. With the development of materials science and fabrication technology, the MN transdermal drug delivery technology has been applied and popularized in more and more fields, including chronic illnesses such as arthritis or diabetes, cancer, dermatocosmetology, family planning, and epidemic disease prevention, and has made fruitful achievements. This paper mainly reviews the latest research status of MNs and their fabrication methodology, and summarizes the application of MNs in the treatment of various diseases, as well as the potential to use nanotechnology to develop more intelligent MNs-based drug delivery systems.


Assuntos
Doença Crônica/tratamento farmacológico , Sistemas de Liberação de Medicamentos/instrumentação , Administração Cutânea , Desenho de Equipamento , Humanos , Microinjeções
6.
Lancet ; 399(10328): 909-923, 2022 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248186

RESUMO

BACKGROUND: Gefapixant is an oral P2X3 receptor antagonist that has previously shown efficacy and safety in refractory chronic cough and unexplained chronic cough. We therefore aim to confirm the efficacy and safety of gefapixant in participants with refractory chronic cough and unexplained chronic cough. METHODS: COUGH-1 and COUGH-2 were both double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. COUGH-1 was done in 156 sites in 17 countries and COUGH-2 in 175 sites in 20 countries. We enrolled participants who were 18 years or older with a diagnosis of refractory chronic cough or unexplained chronic cough of 1 year duration or more. Participants were also required to have a cough severity visual analogue scale score of 40 mm or more at screening and baseline. Eligible participants were randomly allocated (1:1:1), using a computer-generated allocation schedule, to one of three treatment groups: placebo, gefapixant 15 mg twice per day, or gefapixant 45 mg twice per day. All study treatments were given orally. Participants were treated over a 12-week main study period in COUGH-1 and a 24-week main study period in COUGH-2; followed by extension periods for a total of up to 52 weeks of treatment in both trials. The primary outcome was placebo-adjusted mean change in 24-h cough frequency at 12 weeks in COUGH-1 and 24 weeks in COUGH-2. Both studies were registered with ClinicalTrials.gov, NCT03449134 (COUGH-1) and NCT03449147 (COUGH-2). FINDINGS: From March 14, 2018, (first participant screened) to July 26, 2019, (last participant screened) 732 patients were recruited in COUGH-1 and 1317 in COUGH-2. COUGH-1 randomly assigned and treated 730 participants (243 [33×3%] with placebo, 244 [33×4%] with gefapixant 15 mg twice per day, and 243 [33×3%] with gefapixant 45 mg twice per day); COUGH-2 randomly assigned and treated 1314 participants (435 [33×1%] with placebo, 440 [33×5%] with gefapixant 15 mg twice per day, and 439 [33×4%] with gefapixant 45 mg twice per day). Participants were mostly female (542 [74×2%] of 730 in COUGH-1 and 984 [74×9%] of 1314 in COUGH-2). The mean age was 59×0 years (SD 12×6) in COUGH-1 and 58×1 years (12×1) in COUGH-2, and the mean cough duration was 11·6 years (SD 9·5) in COUGH-1 and 11·2 years (9·8) in COUGH-2. Gefapixant 45 mg twice per day showed significant reductions in 24-h cough frequency compared with placebo at week 12 in COUGH-1 (18·5% [95% CI 32·9-0·9]; p=0·041) and at week 24 in COUGH-2 (14·6% [26·1-1·4]; p=0·031). Gefapixant 15 mg twice per day did not show a significant reduction in cough frequency versus placebo in both studies. The most common adverse events were related to taste disturbance: ageusia (36 [4·9%] of 730 in COUGH-1 and 86 [6·5%] of 1314 in COUGH-2), dysgeusia (118 [16·2%] in COUGH-1 and 277 [21·1%] in COUGH-2), hypergeusia (3 [0·4%] in COUGH-1 and 6 [0×5%] in COUGH-2), hypogeusia (19 [2·6%] in COUGH-1 and 80 [6·1%] in COUGH-2), and taste disorder (28 [3·8%] in COUGH-1 and 46 [3·5%] in COUGH-2). INTERPRETATION: Gefapixant 45 mg twice per day is the first treatment to show efficacy with an acceptable safety profile in phase 3 clinical trials for refractory chronic cough or unexplained chronic cough. FUNDING: Merck Sharp & Dohme.


Assuntos
Tosse/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Adulto Jovem
7.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055022

RESUMO

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides' pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.


Assuntos
Biguanidas/química , Biguanidas/farmacologia , Ácidos e Sais Biliares/química , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanomedicina Teranóstica , Doença Crônica/tratamento farmacológico , Desenvolvimento de Medicamentos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Metformina/administração & dosagem , Metformina/farmacocinética , Nanomedicina Teranóstica/métodos
8.
PLoS Negl Trop Dis ; 16(1): e0009192, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35030165

RESUMO

BACKGROUND: Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. METHODS: E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. RESULTS: E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. CONCLUSIONS AND SIGNIFICANCE: AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.


Assuntos
Albendazol/uso terapêutico , Equinococose Hepática/tratamento farmacológico , Echinococcus multilocularis , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Animais , Anticestoides/uso terapêutico , Doença Crônica/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
9.
J Manag Care Spec Pharm ; 28(1): 7-15, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34949113

RESUMO

BACKGROUND: High-deductible health plans (HDHPs) are characterized by higher deductibles and lower monthly premiums compared with a typical health plan. HDHPs may reduce, or delay, needed care, which will ultimately lead to poorer access to care for chronically affected participants. OBJECTIVES: To (1) investigate the HDHP enrollment trend and (2) determine the effects of HDHPs on financial access problems for individuals with self-reported cognitive impairment. METHODS: Data between 2010 and 2018 were obtained from the National Health Interview Survey (NHIS). Individuals with cognitive impairment were identified if they were limited by memory difficulties. Problems regarding financial access to health care were assessed based on 6 survey questions from the Centers for Disease Control and Prevention. Multivariable logistic regressions were implemented to evaluate the effects of HDHPs. RESULTS: This study identified 1,148 individuals with cognitive impairment, representing 3.9 million individuals in the United States from 2010 to 2018. A nearly 2-fold increase in HDHP enrollment with cognitive impairment was observed from 2010 (20.9%) to 2018 (41.9%). This increase is similar to that reported for noncognitively impaired individuals. After controlling for possible confounding variables, cognitively impaired individuals with HDPHs were more likely to have overall financial access difficulties compared with those without HDHPs (OR = 1.17, 95% CI = 0.88-1.56, P = 0.271), but this likelihood was not statistically significant. CONCLUSIONS: HDHPs are intended to support effective care options and reduce health care costs. However, our research found that among individuals with cognitive impairment, those with HDHPs experienced some financial access problems, such as affording medical care, follow-up care, and specialists, than those without HDHPs, indicating that HDHPs might have unintended consequences for health care usage. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest or financial interests to disclose.


Assuntos
Disfunção Cognitiva , Dedutíveis e Cosseguros/economia , Dedutíveis e Cosseguros/tendências , Seguro Saúde/economia , Seguro Saúde/tendências , Adolescente , Adulto , Doença Crônica/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Feminino , Acesso aos Serviços de Saúde/economia , Acesso aos Serviços de Saúde/tendências , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
10.
Mol Metab ; 55: 101409, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863942

RESUMO

BACKGROUND: Chronic disease appears connected to obesity. However, evidence suggests that chronic metabolic diseases are more specifically related to adipose dysfunction rather than to body weight itself. SCOPE OF REVIEW: Further study of the first generation "insulin sensitizer" pioglitazone and molecules based on its structure suggests that is possible to decouple body weight from the metabolic dysfunction that drives adverse outcomes. The growing understanding of the mechanism of action of these agents together with advances in the pathophysiology of chronic metabolic disease offers a new approach to treat chronic conditions, such as type 2 diabetes, fatty liver disease, and their common organ and vascular sequelae. MAJOR CONCLUSIONS: We hypothesize that treating adipocyte dysfunction with new insulin sensitizers might significantly impact the interface of infectious disease and chronic metabolic disease.


Assuntos
Doença Crônica/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Tiazolidinedionas/farmacologia , Tecido Adiposo/metabolismo , COVID-19 , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Inflamação , Insulina/metabolismo , Resistência à Insulina , Doenças Metabólicas/metabolismo , Mitocôndrias , Hepatopatia Gordurosa não Alcoólica , Pioglitazona/metabolismo
11.
Rev. bras. hipertens ; 29(3): 65-68, set. 2022.
Artigo em Português | LILACS | ID: biblio-1517574

RESUMO

As doenças cardiovasculares são a principal causa de morte e de incapacidade no mundo, com destaque para a hipertensão arterial sistêmica (HAS) como um dos principais fatores de risco. No manejo do paciente com HAS, um dos maiores desafios da prática clinica é a aderência ao tratamento. Tal fato se torna mais desafiador ainda em se tratando de doença crônica e na maioria das vezes assintomática. A falta de adesão ao tratamento ocasiona um mau controle da pressão arterial assim como também se associa a lesões de órgão-alvo, eventos cardiovasculares e morte. Fatores como complexidade do regime terapêutico, desconhecimento sobre a doença e suas complicações, sobrecarga da equipe assistencial e polifarmácia são barreiras importantes à aderência adequada. Entre as potenciais ferramentas a fim de mitigar este problema estão esquemas de medicamentos uma vez ao dia em comprimidos únicos, envolvimento da equipe multidisciplinar e uso de tecnologia digital.O entendimento amplo dos fatores que podem impactar a aderência pode melhorar o cuidado aos pacientes com HAS, com o objetivo de melhorar a qualidade de vida e sobrevida e reduzir a sobrecarga ao sistema de saúde (AU).


Cardiovascular diseases are the main cause of death and disability worldwide, being systemic hypertension among the main risk factors. In the management of patients with hypertension, one of the biggest challenges in clinical practice is treatment adherence. This fact is even more challenging considering the chronic and mostly assymptomatic nature of the disease. The lack of adherence to treatment not only results in poor control of blood pressure but also is associated with target-organ lesion, cardiovascular events and death. Factors such as therapeutic regimen complexity, lack of knowledge about disease complications, excess workload to heatlhcare professionals and polypharmacy are important barriers to adequate adherence. Among the potential tools that are available to mitigate this problem are single pill, once a day regimens; multidisciplinary approach; and digital technologies. The broad understanding of factors that may impact treatment adherence can improve care of patients with hypertension, with the goal of improving quality of life, prolonging survival and decreasing the burden to the health system


Assuntos
Humanos , Doença Crônica/tratamento farmacológico , Adesão à Medicação , Fatores de Risco de Doenças Cardíacas , Hipertensão/tratamento farmacológico
12.
São Paulo; s.n; 2022. 42 p. tab.
Tese em Português | HomeoIndex - Homeopatia | ID: biblio-1380169

RESUMO

Há poucos estudos sobre a eficácia do tratamento homeopático na diarréia crônica, por isso relatos de casos são os primeiros degraus da evidência clínica [1]. As pesquisas utilizando medicamentos altamente diluídos têm avançado significativamente e a Medicina sempre está em busca de novas abordagens terapêuticas. Sendo a Homeopatia uma possibilidade no tratamento devido à sua alta resolutividade e baixo custo, comentamos sobre este tema que vem assumindo a cada dia mais importância na sociedade, devido aos impactos que provoca. Este relato de caso tem como objetivo principal apresentar o tratamento Unicista orientado por Hahnemann. Apresentamos o caso de uma paciente adulta que procurou consulta homeopática por diarréia crônica, após longo período de tratamento alopático sem resolução. Relatamos o atendimento, a repertorização e o tratamento com o medicamento policresto Phosphorus (simillimum da paciente). Demonstramos o surpreendente resultado obtido com o tratamento, respeitando a individualidade da paciente e observando os fundamentos da Homeopatia. Concluímos que a atuação do médico tem importância relevante na condução do tratamento e na melhora de qualidade de vida do seu paciente, e que a Homeopatia é uma grande aliada ao minimizar os danos deste transtorno. A cura de uma doença pode ser feita com tratamento homeopático Unicista segundo os ensinamentos do Pai da Homeopatia.


There are few studies on the effectiveness of homeopathic treatment in Chronic Diarrhea, so case reports are the first steps of clinical evidence. Researchs using highly diluted drugs has advanced significantly. Considering a challenge, Medicine is looking for new therapeutic approaches and Homeopathy is a possibility in the treatment due to its high resolution and low cost. We briefly comment on this topic, which is becoming increasingly important in society, due to the impacts it causes. This case report has as main objective to present the homeopathic treatment in a Unicist way according to the guidelines of Hahnemann. In the patient's search for homeopathy, we studied the case, performed the repertorization and found Phosphorus as the patient's simillimum. We demonstrate the surprising result obtained with the homeopathic treatment, respecting the patient's individuality and observing the fundamentals of Homeopathy. We conclude that the doctor's performance has relevant importance in the conduct of the treatment and in the improvement of the patient's quality of life, and that homeopathy is a great ally in minimizing the damage of this disorder. The cure of a disease can be done with Unicist homeopathic treatment according to the teachings of the Father of Homeopathy.


Assuntos
Humanos , Feminino , Idoso , Fósforo/uso terapêutico , Unicismo , Doença Crônica/tratamento farmacológico , Diarreia/tratamento farmacológico , Antidiarreicos/uso terapêutico
13.
Braz. J. Pharm. Sci. (Online) ; 58: e20956, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1420488

RESUMO

Abstract The insertion of Pharmaceutical Care in Primary Health Care (PHC) improves patients' clinical outcomes and quality of life. Pharmacotherapeutic follow-up can contribute to the management of chronic diseases such as diabetes, promoting better glycemic control and adherence to therapy. This study aimed to assess the Drug-therapy Problems (DTPs) and Pharmacist Interventions (PIs) on the pharmacotherapeutic management in patients with type 2 diabetes mellitus (T2DM) in a community pharmacy. A quantitative, retrospective, and cross-sectional study was conducted in a Pharmaceutical Care Program within the PHC in Juiz de Fora (Minas Gerais, Brazil). Inclusion criteria were patients with T2DM above 18, who attended at least three pharmaceutical consultations between July 2016 and October 2018 and presented two or more glycated hemoglobin tests. The study group (n = 17) was largely composed of women (65%), elderly (76%), sedentary (72%), and obese people (52%). The resolution was achieved in 79% of the DTPs identified (n = 115). Most of DTPs were related to administration and adherence to pharmacotherapy (46%). 60% of the 437 PIs involved the provision of information and counseling. In other words, accessible interventions lead to high resolvability. Therefore, clinical actuation of pharmacists could improve the prognosis in diabetes treatment


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Pacientes/classificação , Assistência Farmacêutica/organização & administração , Atenção Primária à Saúde/organização & administração , Diabetes Mellitus Tipo 2/patologia , Farmácias/classificação , Encaminhamento e Consulta/normas , Doença Crônica/tratamento farmacológico , Estudos Transversais/instrumentação , Farmacoepidemiologia/instrumentação , Tratamento Farmacológico/classificação
14.
PLoS One ; 16(12): e0261032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34882708

RESUMO

BACKGROUND: Commonly used medications produce changes in the gut microbiota, however, the impact of these medications on the composition of the oral microbiota is understudied. METHODS: Saliva samples were obtained from 846 females and 368 males aged 35-69 years from a Canadian population cohort, the Atlantic Partnership for Tomorrow's Health (PATH). Samples were analyzed by 16S rRNA gene sequencing and differences in microbial community compositions between nonusers, single-, and multi-drug users as well as the 3 most commonly used medications (thyroid hormones, statins, and proton pump inhibitors (PPI)) were examined. RESULTS: Twenty-six percent of participants were taking 1 medication and 21% were reported taking 2 or more medications. Alpha diversity indices of Shannon diversity, Evenness, Richness, and Faith's phylogenetic diversity were similar among groups, likewise beta diversity as measured by Bray-Curtis dissimilarity (R2 = 0.0029, P = 0.053) and weighted UniFrac distances (R2 = 0.0028, P = 0.161) were non-significant although close to our alpha value threshold (P = 0.05). After controlling for covariates (sex, age, BMI), six genera (Saprospiraceae uncultured, Bacillus, Johnsonella, Actinobacillus, Stenotrophomonas, and Mycoplasma) were significantly different from non-medication users. Thyroid hormones, HMG-CoA reductase inhibitors (statins) and PPI were the most reported medications. Shannon diversity differed significantly among those taking no medication and those taking only thyroid hormones, however, there were no significant difference in other measures of alpha- or beta diversity with single thyroid hormone, statin, or PPI use. Compared to participants taking no medications, the relative abundance of eight genera differed significantly in participants taking thyroid hormones, six genera differed in participants taking statins, and no significant differences were observed with participants taking PPI. CONCLUSION: The results from this study show negligible effect of commonly used medications on microbial diversity and small differences in the relative abundance of specific taxa, suggesting a minimal influence of commonly used medication on the salivary microbiome of individuals living without major chronic conditions.


Assuntos
Bactérias/isolamento & purificação , Doença Crônica/tratamento farmacológico , Microbiota/efeitos dos fármacos , Preparações Farmacêuticas/administração & dosagem , RNA Ribossômico 16S/genética , Saliva/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Canadá/epidemiologia , Estudos de Casos e Controles , Doença Crônica/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Saliva/efeitos dos fármacos
15.
PLoS One ; 16(12): e0261264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34914757

RESUMO

BACKGROUND: The objectives of this study were; (I) to determine the proportion of pathogens isolated from patients with infected chronic wounds in the surgical ward of MRRH that are resistant to the third-generation cephalosporins and (II) to determine the factors associated with resistance to third-generation cephalosporins in the surgical ward of MRRH. METHOD(S): This study was a descriptive analytical survey of bacterial isolates from infected chronic wounds among patients admitted in the surgical ward of MRRH, Uganda. Seventy five (75) study participants were recruited in the study using convenient sampling technique. Bacterial culture and identification was performed using standard microbiology laboratory procedures whereas broth microdilution method was used to establish the susceptibility of the identified pathogens. Data for objective one (1) was summarized as proportions while the categorized variables were analyzed using logistic regression to determine whether they were associated with the resistance patterns. The level of significance was preset at 5% and p-values less than 0.05 were considered statistically significant. RESULTS: Generally, all isolates had complete susceptibility (100%) to Cefoperazone+Sulbactam 2g except 7.1% of proteus spp that were resistant. Of all the bacterial isolates studied, Staphylococcus aureus, Enterobacter agglomerans, providencia spp and pseudomonas earuginosa had complete resistance (100%) to Cefopodoxime 200mg while providencia spp and pseudomomas earuginosa had complete resistance (100%) to Cefixime 400mg and cefotaxime 1g. Finally, higher odds of bacterial resistance to more 2 brands of the third generation cephalosporins were observed among participants who had prior exposure to the third generation cephalosporins (OR, 2.22, 95% CI, 0.80-6.14), comorbidities (OR, 1.76, 95% CI, 0.62-4.96) and those who had more than two hospitalizations in a year (OR, 1.39, 95% CI 0.46-4.25). However, multivariate logistic regression was not performed since no factor was significantly associated with resistance to more than two brands of third generation cephalosporins (p >0.05). CONCLUSION: This study found that cefixime and cefpodoixme had high rates of resistance and should not be used in routine management of infected chronic wounds. In addition, the factors investigated in this study were not significantly associated with bacterial resistance to more than two brands of third generation cephalosporins.


Assuntos
Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana/fisiologia , Infecção dos Ferimentos/tratamento farmacológico , Adulto , Idoso , Antibacterianos/uso terapêutico , Cefixima/farmacologia , Cefoperazona/uso terapêutico , Ceftizoxima/análogos & derivados , Ceftizoxima/farmacologia , Doença Crônica/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Hospitais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sulbactam/uso terapêutico , Uganda/epidemiologia , Infecção dos Ferimentos/microbiologia
16.
Molecules ; 26(23)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34885693

RESUMO

Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.


Assuntos
Doença Crônica/tratamento farmacológico , Curcumina/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Disponibilidade Biológica , Doença Crônica/prevenção & controle , Curcumina/análogos & derivados , Curcumina/química , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanotecnologia , Solubilidade
17.
Sci Rep ; 11(1): 22521, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795324

RESUMO

Peptide therapeutics are increasingly used in the treatment of disease, but their administration by injection reduces patient compliance and convenience, especially for chronic diseases. Thus, oral administration of a peptide therapeutic represents a significant advance in medicine, but is challenged by gastrointestinal instability and ineffective uptake into the circulation. Here, we have used glucagon-like peptide-1 (GLP-1) as a model peptide therapeutic for treating obesity-linked type 2 diabetes, a common chronic disease. We describe a comprehensive multidisciplinary approach leading to the development of MEDI7219, a GLP-1 receptor agonist (GLP-1RA) specifically engineered for oral delivery. Sites of protease/peptidase vulnerabilities in GLP-1 were removed by amino acid substitution and the peptide backbone was bis-lipidated to promote MEDI7219 reversible plasma protein binding without affecting potency. A combination of sodium chenodeoxycholate and propyl gallate was used to enhance bioavailability of MEDI7219 at the site of maximal gastrointestinal absorption, targeted by enteric-coated tablets. This synergistic approach resulted in MEDI7219 bioavailability of ~ 6% in dogs receiving oral tablets. In a dog model of obesity and insulin resistance, MEDI7219 oral tablets significantly decreased food intake, body weight and glucose excursions, validating the approach. This novel approach to the development of MEDI7219 provides a template for the development of other oral peptide therapeutics.


Assuntos
Doença Crônica , Sistemas de Liberação de Medicamentos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos , Engenharia de Proteínas , Animais , Cricetinae , Humanos , Masculino , Camundongos , Administração Oral , Células CACO-2 , Química Farmacêutica/métodos , Ácido Quenodesoxicólico/administração & dosagem , Células CHO , Doença Crônica/tratamento farmacológico , Cricetulus , Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Células Secretoras de Insulina/citologia , Camundongos Endogâmicos C57BL , Peptídeos/química , Galato de Propila/administração & dosagem , Engenharia de Proteínas/métodos , Receptores de Glucagon/agonistas , Comprimidos com Revestimento Entérico
18.
PLoS Negl Trop Dis ; 15(11): e0009978, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34784372

RESUMO

BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapeutic agent to regulate the pro-inflammatory state during the early chronic phase of Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 µg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 µg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the early chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue. CONCLUSIONS/SIGNIFICANCE: AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during early chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/administração & dosagem , Animais , Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/parasitologia , Doença Crônica/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Coração/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/imunologia , Nitroimidazóis/administração & dosagem , Carga Parasitária , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/imunologia , Trypanosoma cruzi/fisiologia
19.
PLoS One ; 16(11): e0260112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34784405

RESUMO

BACKGROUND: Older adults with chronic conditions are at high risk of complications from influenza and pneumococcal infections. Evidence about factors associated with influenza and pneumococcal vaccination among older multimorbid persons in Europe is limited. The aim of this study was to investigate the prevalence and determinants of these vaccinations in this population. METHODS: Multimorbid patients aged ≥70 years with polypharmacy were enrolled in 4 European centers in Switzerland, Belgium, the Netherlands, and Ireland. Data on vaccinations, demographics, health care contacts, and comorbidities were obtained from self-report, general practitioners and medical records. The association of comorbidities or medical contacts with vaccination status was assessed using multivariable adjusted log-binomial regression models. RESULTS: Among 1956 participants with available influenza vaccination data (median age 79 years, 45% women), 1314 (67%) received an influenza vaccination within the last year. Of 1400 patients with available pneumococcal vaccination data (median age 79 years, 46% women), prevalence of pneumococcal vaccination was 21% (n = 291). The prevalence of vaccination remained low in high-risk populations with chronic respiratory disease (34%) or diabetes (24%), but increased with an increasing number of outpatient medical contacts. Chronic respiratory disease was independently associated with the receipt of both influenza and pneumococcal vaccinations (prevalence ratio [PR] 1.09, 95% confidence interval [CI] 1.03-1.16; and PR 2.03, 95%CI 1.22-3.40, respectively), as was diabetes (PR 1.06, 95%CI 1.03-1.08; PR 1.24, 95%CI 1.16-1.34, respectively). An independent association was found between number of general practitioner visits and higher prevalence of pneumococcal vaccination (p for linear trend <0.001). CONCLUSION: Uptake of influenza and particularly of pneumococcal vaccination in this population of European multimorbid older inpatients remains insufficient and is determined by comorbidities and number and type of health care contacts, especially outpatient medical visits. Hospitalization may be an opportunity to promote vaccination, particularly targeting patients with few outpatient physician contacts.


Assuntos
Doença Crônica/tratamento farmacológico , Vacinas contra Influenza/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Vacinação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Bélgica/epidemiologia , Doença Crônica/classificação , Doença Crônica/epidemiologia , Estudos Transversais , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Irlanda/epidemiologia , Masculino , Multimorbidade , Países Baixos/epidemiologia , Polimedicação/estatística & dados numéricos , Prevalência , Fatores de Risco , Autorrelato , Suíça/epidemiologia
20.
Value Health ; 24(10): 1520-1530, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34593176

RESUMO

OBJECTIVES: Although there is a growing body of evidence suggesting that cannabinoids may relieve symptoms of some illnesses, they are relatively high-cost therapies compared with illicit growth and supply. This article aimed to comprehensively review economic evaluations of medicinal cannabis for alleviating refractory symptoms associated with chronic conditions. METHODS: Seven electronic databases were searched for articles published up to September 6, 2020. The quality of reporting of economic evaluations was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. The extracted data were grouped into subcategories according to types of medical conditions, organized into tables, and reported narratively. RESULTS: This review identified 12 cost-utility analyses conducted across a variety of diseases including multiple sclerosis (MS) (N = 8), pediatric drug-resistant epilepsies (N = 2), and chronic pain (N = 2). The incremental cost-effectiveness ratio varied widely from cost saving to more than US$451 800 per quality-adjusted life-year depending on the setting, perspectives, types of medicinal cannabis, and indications. Nabiximols is a cost-effective intervention for MS spasticity in multiple European settings. Cannabidiol was found to be a cost-effective for Dravet syndrome in a Canadian setting whereas a cost-utility analysis conducted in a US setting deemed cannabidiol to be not cost-effective for Lennox-Gastaut syndrome. Overall study quality was good, with publications meeting 70% to 100% (median 83%) of the Consolidated Health Economic Evaluation Reporting Standards checklist criteria. CONCLUSIONS: Medicinal cannabis-based products may be cost-effective treatment options for MS spasticity, Dravet syndrome, and neuropathic pain, although the literature is nascent. Well-designed clinical trials and health economic evaluations are needed to generate adequate clinical and cost-effectiveness evidence to assist in resource allocation.


Assuntos
Doença Crônica/tratamento farmacológico , Análise Custo-Benefício/métodos , Maconha Medicinal/normas , Canadá , Análise Custo-Benefício/estatística & dados numéricos , Humanos , Maconha Medicinal/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/fisiopatologia
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