La prescription de médicament hors AMM est légitime quand elle s’appuie sur les connaissances médicales acquises ou validées au moment de la proposition de soins, lors du colloque singulier patient-médecin. L’AMM d’un médicament ne représente qu’un sous-ensemble de connaissances médicales, sans cesse changeantes, qui ne peut être regardée comme le référentiel idoine de la prescription d’un médicament, à la fois sur un plan médical et sur un plan juridique. La démocratie sanitaire est particulièrement inachevée dans la gestion européenne ou nationale de l’AMM d’un médicament. / The off-label drug prescribing is legitimate when it is based on accepted or validated medical knowledge at the time of the proposal care during the patient-physician singular interview. The marketing authorization of a drug represents only a fraction of medical knowledge, constantly changing, which can not be considered as a suitable reference document of drug prescribing, both from a medical and legal aspect. Health democracy is particularly incomplete in the European or national management of the drug marketing authorization.

Introdução. Desde a promulgação da Constituição Federal de 1988 no Brasil, que consolida a saúde como um direito social, a ser garantido de forma integral e universal pelo Estado brasileiro, os cidadãos passaram a reivindicar este direito em juízo, acionando legitimamente o Estado para a garantia de suas pretensões sanitárias. E, neste sentido, o número de ações que demandam medicamentos vem crescendo de forma exponencial no Brasil, impactando diretamente a política pública de saúde, e suscitando debates sobre a segurança sanitária dos medicamentos dispensados em juízo. Objetivo. Evidenciar de que forma as questões técnicas e políticas que envolvem o direito social à assistência farmacêutica vem sendo debatidas dentro de processos judiciais que tem por objeto a solicitação de medicamentos em face do Estado. Isto para que se possa relacionar estes resultados aos atuais debates sobre o papel do Poder Judiciário em face da garantia do direito à saúde, e seu impacto perante a política pública de saúde. E, também, aos atuais debates político-sanitários sobre a prescrição médica, e sua importância para o exercício do direito em foco. Método. A metodologia de pesquisa revestiu-se em duas etapas distintas. A primeira etapa consistiu na análise de processos judiciais que versavam sobre a demanda de medicamentos em face do Estado, provenientes de quatro Tribunais Estaduais do país, em primeira instância: São Paulo, Minas Gerais, Rio Grande do Sul e Rio de Janeiro. Os processos foram analisados através do uso da Metodologia Qualiquantitativa do Discurso Coletivo. A segunda etapa consistiu na pesquisa de artigos científicos, nas principais bases de dados de periódicos científicos de saúde pública, que tivessem relação com a pergunta de pesquisa: Como hoje estrutura-se a discussão político-sanitária em torno da prescrição médica? Resultados. Pela análise dos processos judiciais, evidencia-se que as demandas que envolvem pedidos de medicamento em juízo vêm sendo deferidas pelos juízes, prioritariamente, com base nas prescrições médicas individuais e com base na leitura pura do ordenamento jurídico, sem considerar as dimensões técnicas e políticas que envolvem o direito à assistência farmacêutica. A análise dos artigos científicos nos demonstra a vasta discussão técnica acerca da prescrição médica e suas implicações sanitárias, e aponta a necessidade de contraditar esses documentos e investir em educação e informação médicas, em prol da segurança sanitária dos pacientes-cidadãos. Conclusão. O direito à saúde é um direito complexo, que requer, para a sua adequada proteção e garantia, que ultrapassemos o paradigma positivista, com sua leitura exclusivamente normativa e dogmática, em prol de um novo paradigma que permita maior penetração de questões e saberes técnicos e políticos no âmbito do direito. Tanto judicial quanto extrajudicialmente precisam ser criados caminhos de proteção à saúde, que abriguem todos os profissionais jurídicos, políticos e técnicos envolvidos na temática, rumo à construção interdisciplinar do direito à saúde e da cidadania sanitária no Brasil / Introduction. Since the enactment of the 1988 Federal Constitution in Brazil, that consolidates health as a social right, the citizens began to demand this right in court, lawfully driving the state to guarantee their health claims. And, in this sense, the number of actions that require medicines is growing exponentially in Brazil, which impact directly the public health policy, and stimulate discussions about the safety of drugs dispensed by the courts. Objective. Show how the technical and political issues, involving the social right to pharmaceutical assistance has been debated in legal proceedings whose objective is the solicitation of drugs against the State. This to be able to relate these findings to the current debates about the role of the judiciary, in view of the guaranteed of right to health and its impact on the public health policy. And, also, to the current political debates about health prescription, and its importance for the right in focus. Method. The research methodology is coated in two stages. The first step was the analysis of court cases that focused the drug demand against the State, from Four State Courts in Brazil: Sao Paulo, Minas Gerais, Rio Grande do Sul and Rio de Janeiro. The processes were analyzed through the use of qualitativequantitative methodology of collective discourse. The second step consisted in the search of scientific articles in major databases of scientific journals of public health, that were related to the following research question: How today\'s discussion is structured around the political health context of the medical prescription? Results. The analysis of court proceedings, results clear that the demands that involve medication in court have been deferred by the judges, primarily, based on the individual medical prescriptions, and based on the pure reading of the legal system, without considering the technical and political dimensions that involve the right to pharmaceutical assistance. The analysis of scientific articles shows us the extensive technical discussion about the prescription and its health implications, and highlights the need to contradict these documents, and invest in education and medical information, towards the safety of patients-citizens. Conclusion. The right to health is a complex right, which requires for its adequate protection and security, that we move beyond the positivist paradigm, with its exclusively normative reading and dogmatic rules, towards a new paradigm which allows greater penetration of issues and political and technical knowledge within the law. Both judicial and extrajudicial ways need to be created to protect health, involving all legal, politicians and technicians professionals involved in the matter, toward interdisciplinary construction of the right to health and health citizenship in Brazil

Chapter 1 reviews better-known factorization theorems of a square matrix. For example, a square matrix over a field can be expressed as a product of two symmetric matrices; thus square matrices over real numbers can be factorized into two diagonalizable matrices. Factorizing matrices over complex num hers into Hermitian matrices is discussed. The chapter concludes with theorems that enable one to prescribe the eigenvalues of the factors of a square matrix, with some degree of freedom. Chapter 2 proves that a square matrix over arbitrary fields (with one exception) can be expressed as a product of two diagona lizab le matrices. The next two chapters consider decomposition of singular matrices into Idempotent matrices, and of nonsingutar matrices into Involutions. Chapter 5 studies factorization of a comp 1 ex matrix into Positive-( semi )definite matrices, emphasizing the least number of such factors required / Mathematical Sciences / M.Sc. (MATHEMATICS)

Chapter 1 reviews better-known factorization theorems of a square matrix. For example, a square matrix over a field can be expressed as a product of two symmetric matrices; thus square matrices over real numbers can be factorized into two diagonalizable matrices. Factorizing matrices over complex numbers into Hermitian matrices is discussed. The chapter concludes with theorems that enable one to prescribe the eigenvalues of the factors of a square matrix, with some degree of freedom. Chapter 2 proves that a square matrix over arbitrary fields (with one exception) can be expressed as a product of two diagonalizable matrices. The next two chapters consider decomposition of singular matrices into Idempotent matrices, and of nonsingular matrices into Involutions. Chapter 5 studies factorization of a complex matrix into Positive-(semi)definite matrices, emphasizing the least number of such factors required. / Mathematical Sciences / M. Sc. (Mathematics)

INTRODUÇÃO: A Tuberculose (TB) e a Síndrome da Imunodeficiência Adquirida (AIDS) são, individualmente, grandes ameaças à saúde pública. As epidemias de AIDS e TB são sinérgicas e criaram uma crise de grandes proporções e desafios para o manejo clínico dos doentes, serviços de saúde e órgãos governamentais. A infecção pelo Vírus da Imunodeficiência Humana (HIV) é um dos principais fatores de risco para TB. O tratamento de pacientes com HIV ou aids e TB requer o uso concomitante de medicamentos tuberculostáticos e antirretrovirais, e as dificuldades a serem superadas incluem alto número de comprimidos, adesão aos tratamentos, interações medicamentosas com possibilidade de sobreposição de efeitos tóxicos e síndrome de reconstituição imune inflamatória. Uma forma de prevenção da TB é o Tratamento Preventivo com Isoniazida (TPI) nos pacientes com Infecção Latente por Mycobacterium tuberculosis (ILMTb), para os quais taxas de adesão de 80% ou mais são adequadas. A baixa adesão ao TPI diminui a sua efetividade. Neste cenário, avaliar a adesão ao TPI é de grande importância. O Serviço de Farmácia pode ser um instrumento altamente eficiente para realizar esta avaliação, através do acompanhamento das taxas de dispensação de isoniazida (INH) prescrita como TPI. OBJETIVO: Avaliar a taxa de adesão ao TPI em sujeitos com HIV ou aids e ILMTb, através da dispensação de INH. MÉTODO: Foram incluídos sujeitos que apresentaram prescrição do medicamento INH no período de 01/07/2008 a 30/06/2011 na farmácia do Serviço de Extensão ao Atendimento de Pacientes HIV/Aids da Divisão de Moléstias Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (SEAP HIV/Aids). As informações sobre sexo, idade, acompanhamento médico, uso de antirretrovirais, doenças concomitantes, intercorrências, datas de início e término do TPI foram obtidas do prontuário e informações sobre prescrição e dispensação de INH foram obtidas do Sistema de Informações de Gerenciamento Hospitalar (SIGH). RESULTADOS: Foram incluídos na análise 161 sujeitos, 78,9% (127) do sexo masculino, com idade média de 46 anos, 84,5% (136) deles acompanhados por médicos assistentes, 92,5% (149) utilizavam drogas antirretrovirais, 77,6% (125) apresentavam doenças concomitantes e 12,4% (20) sofreram intercorrências durante o TPI. Observou-se aumento transitório de enzimas hepáticas que não justificava a suspensão do TPI. A taxa de adesão foi de 96%. A prescrição eletrônica da INH nem sempre acompanhou, temporalmente, as datas, registradas em prontuário, de início e fim do TPI. A análise de concomitância entre início e fim do TPI e a prescrição de INH foi realizada para 90% (146) dos sujeitos para os quais estas informações eram disponíveis. Para 8,7% (14) dos sujeitos a prescrição eletrônica foi posterior à data de início de TPI; para 56,2% (82) dos sujeitos a prescrição de INH ultrapassou a data de término do TPI no prontuário e para 17,1% (25) dos sujeitos a prescrição de INH foi encerrada antes do término do TPI no prontuário. Não foram observadas associações estatísticas significativas entre o desfecho e as variáveis de interesse. CONCLUSÃO: Adesão é um comportamento complexo, assim como sua avaliação. Identificamos elevada taxa de adesão ao TPI entre sujeitos que vivem com HIV/aids; a frequência de hepatotoxicidade foi baixa e, quando ocorreu, transitória. Salientamos o descompasso entre o projeto terapêutico de TPI, registrado em prontuário, e a sua concretização, através da prescrição da INH. A prescrição eletrônica é um instrumento concebido para elevar a qualidade e agilizar a assistência; entretanto, pode expor o paciente a prescrição inadequada. Para evitá-lo devem ser adotadas medidas de segurança que, sem dificultar a prescrição, possam aprimorá-la constantemente, conforme os protocolos de tratamento disponíveis e os conhecimentos atualizados / BACKGROUND: Tuberculosis (TB) and Acquired Immunodeficiency Syndrome (AIDS) are major threats to public health. The Aids and TB epidemics are synergistic, bring great challenges for the clinical management of patients, health services and governments. Infection with Human Immunodeficiency Virus (HIV) is a major risk for TB. The treatment of coinfected patients requires antituberculosis and antiretroviral drugs administered concomitantly. These patients are defied by the high number of tablets, adherence, drugs interactions, overlapping toxicities and immune reconstitution inflammatory syndrome. The isoniazid preventive therapy (IPT) is recommended to reduce the risk of TB in HIV/aids patients with Mycobacterium tuberculosis Latent Infection (MTbLI). Adherence rates of 80% or more are adequate. Low adherence to the IPT reduces its effectiveness. Assessing adherence to the IPT is of great importance in this setting, and the withdrawal of INH from the pharmacy can be used for this purpose. OBJECTIVE: To evaluate the adherence to the IPT in subjects with HIV/Aids and MTbLI, followed at Serviço de Extensão ao Atendimento de Pacientes HIV/ Aids (SEAP HIV/Aids), an HIV/aids outpatient clinic, through the withdrawal of INH from the pharmacy. METHODS: subjects with HIV/Aids and MTbLI who had a prescription of INH for IPT from 01/07/2008 to 30/06/2011 were included. Information about sex, age, medical conditions, antiretrovirals, comorbidities, IPT period, intercurrences during the IPT and withdrawal of INH from the pharmacy were retrieved from the medical files and the system of information and hospital management (SIGH). RESULTS: 161 subjects were included in the study, 78,9% (127) of them males, with a mean age of 46 years, 84,5 % (136) of them assisted by infectologists, 92,5% ( 149) taking antiretrovirals, 77,6% (125) with comorbidities and 12,4% (20) with intercurrences during the IPT; a low and transient increase of liver enzymes that not led to discontinuation of the IPT was observed. The adherence rate was 96%. The evaluation of concordance between the periods of ITP and prescription of INH was performed for 90% (146) of subjects for whom this information was available. The electronic prescription of INH was not coincident with the period of IPT registered in medical files for most subjects. To 8,7% (14) of the subjects the electronic prescription was made after the beginning of IPT, for 56,2% (82) of the subjects the prescription of INH exceeded the date of completion of the IPT and for 17,1% (25) of the subjects the prescription of INH ended before the end of the IPT registered in medical files. No statistically significant associations between the outcome and the variables of interest were observed. CONCLUSION: Adherence is a complex behavior, as well as their evaluation. We found a high adherence rate to IPT among HIV/Aids subjects with MTbLI, with a low and transient grade of hepatotoxicity. Although the electronic prescription is an instrument designed to improve the quality of the health care, it can expose patients to inappropriate prescription. To avoid this, security measures should be adopted, in order to improve it constantly, according to the protocols of treatment available and updated knowledge, without hampering medical prescription

Contexte : Les patients âgés atteints de néphropathie diabétique ne reçoivent souvent pas un traitement pharmacologique optimal. Les directives de pratique clinique actuelles n'intègrent pas le concept de soins personnalisés. Les algorithmes d'aide à la décision clinique (ADC) qui tiennent compte à la fois des preuves et des soins personnalisés pour améliorer les résultats des patients peuvent améliorer les soins aux personnes âgées. L'objectif de cette recherche est de concevoir et de valider un algorithme ADC pour la prescription d'inhibiteurs du système rénineangiotensine- aldostérone (ISRAA) pour les patients âgés atteints de diabète. Méthodes : La conception de l'algorithme ADC comprenait trois phases principales. Dans la première phase, nous avons recherché, examiné et évalué les preuves actuelles sur plusieurs sujets liés aux décisions de prescription pour les patients âgés et à l'adhésion des cliniciens aux directives de pratique. Nous avons également procédé à un examen systématique et à une méta-analyse d'essais cliniques randomisés afin de déterminer les valeurs du nombre de patients à traiter (NPT) et du délai d'obtention d'un avantage (DOA) applicables à notre population cible en vue de leur utilisation dans l'algorithme. Dans la deuxième phase, nous avons exploré les points de vue des patients et des prestataires de soins de santé sur les outils ADC en menant des entretiens avec les patients et une enquête transversale auprès des prestataires de soins de santé. Dans la troisième et dernière phase, les résultats des études réalisées dans les phases un et deux ont été utilisés pour informer le développement de l'algorithme ADC qui a ensuite été validé dans une étude Delphi. Résultats : Nous avons créé un algorithme ADC qui couvrait 16 scénarios possibles. Neuf scénarios correspondaient à des recommandations de méta-analyses, tandis que cinq scénarios correspondaient à des directives de pratique clinique. Pour les neuf cas, nous avons généré 36 recommandations personnalisées et neuf recommandations générales sur la base des valeurs NPT et DOA calculées et appariées. En outre, nous avons pris en compte l'espérance de vie et la capacité fonctionnelle du patient. L'algorithme a été validé lors de trois tours d'une étude Delphi. Conclusion : Nous avons conçu un algorithme de CDS fondé sur des preuves qui intègre des considérations souvent négligées dans les directives de pratique clinique, notamment l'espérance de vie restante, la charge médicamenteuse et l'état fonctionnel. Les prochaines étapes consistent à le tester dans le cadre d'un essai clinique afin d'étudier s'il est capable d'atteindre des objectifs cliniques prévisibles et réalistes, de maintenir la qualité de vie des personnes âgées et de réduire l'utilisation et le coût du système de santé. / Background: Older patients with diabetic nephropathy often do not receive optimal pharmacological treatment. Current clinical practice guidelines do not incorporate the concept of personalized care. Clinical decision support (CDS) algorithms that consider both evidence and personalized care to improve patient outcomes can improve the care of older adults. The aim of this research is to design and validate a CDS algorithm for prescribing renin-angiotensin aldosterone system inhibitors (RAASi) for older patients with diabetes. Methods: The design of the CDS algorithm included three main phases. In phase one, we searched, reviewed, and evaluated current evidence on several topics related to prescribing decisions for older patients and clinicians' adherence to practice guidelines. We also conducted a systematic review and a meta-analysis of randomized clinical trials to determine the number needed to treat (NNT) and time-to-benefit (TTB) values applicable to our target population for use in the algorithm. In phase two, we explored the views of patients and healthcare providers on CDS tools through conducting patient interviews and a cross-sectional survey of healthcare providers. In the third and final phase, findings from studies completed in phases one and two were used to inform the development of the CDS algorithm which was then validated using modified Delphi methodology. Results: We have created a CDS algorithm that covered 16 possible scenarios. There were nine scenarios matched to meta-analysis recommendations, while five scenarios were matched to clinical practice guidelines. For the nine cases, we have generated 36 personalized and nine general recommendations based on the calculated and matched NNT and TTB values. In addition, we have considered the patient’s life expectancy and functional capacity. The algorithm was validated in three rounds of a modified Delphi study. Conclusion: We designed an evidenceinformed CDS algorithm that integrates considerations often overlooked in clinical practice guidelines, including remaining life expectancy, medication burden, and functional status. The next steps include testing in a clinical trial to study if it is able to achieve predictable and realistic clinical goals, maintaining quality of life in older adults, and reducing healthcare system use and cost.

No description available.

No description available.

Background: The purpose of drug treatment is to reduce morbidity and mortality, and to improve health-related quality of life. However, there are frequent problems associated with drug treatment, especially among the elderly. The aim of this thesis was to investigate the impact of clinical pharmacy services within a multiprofessional healthcare team on quality and safety of patients’ drug therapy, and to study the frequency and nature of medication history errors on admission to hospital. Methods: A model for clinical pharmacy services within a multiprofessional healthcare team (the Lund Integrated Medicines Management model, LIMM) was introduced in three hospital wards. On admission of patients to hospital, clinical pharmacists conducted medication reconciliation (i.e. identified the most accurate list of a patient’s current medications) to identify any errors in the hospital medication list. To identify, solve and prevent any other drug-related problems, the clinical pharmacists interviewed patients and performed medication reviews and monitoring of drug therapy. Drug-related problems were discussed within the multiprofessional team and the physicians adjusted the drug therapy as appropriate. Results: On admission to hospital, drug-related problems, such as low adherence to drug therapy and concerns about treatment, were identified. Different statistical approaches to present results from ordinal data on adherence and beliefs about medicines were suggested. Approximately half of the patients were affected by errors in the medication history at admission to hospital; patients who had many prescription drugs had a higher risk for errors. Medication reconciliation and review reduced the number of inappropriate medications and reduced drug-related hospital revisits. No impact on all-cause hospital revisits was demonstrated. Conclusion: Patients admitted to hospital are at high risk for being affected by medication history errors and there is a high potential to improve their drug therapy. By reducing medication history errors and improving medication appropriateness, clinical pharmacy services within a multiprofessional healthcare team improve the quality and safety of patients’ drug therapy. The impact of routine implementation of medication reconciliation and review on healthcare visits will need further evaluation; the results from this thesis suggest that drug-related hospital revisits could be reduced. / Läkemedelsgenomgångar och läkemedelsavstämning - LIMM-modellen

There is an identified problem with patients receiving suboptimal pain management at a hospice agency in the northwestern United States. At this agency, undertreatment of pain is prevalent. Evidence indicates that this may be a result of a lack of guidelines, education, and knowledge of appropriate prescribing. Known barriers to the correct prescription and administration of potent opioids in the hospice setting include prevailing beliefs, knowledge, skills, and attitudes, all of which can impact care negatively. Contextually, hospice principles mandate patient comfort and caregiver involvement in continuous quality improvement, which includes adequate and informed pain management. Moreover, hospice metrics demand requisite knowledge, skills, and attitudes for optimal care, including pain management at the end of life. The Academic Center for Evidence-Based Practice (ACE) star model was used to guide the development of an evidence-based, guideline-supported educational program that will improve pain management at the hospice agency when implemented. The purpose of this project was to use transdisciplinary expertise and team collaboration to develop the program and then to conduct a formative and summative evaluation utilizing experts to prepare the guidelines and process for implementation. Ten experts reviewed the guideline, the educational materials, the process, and the evaluation plan and conducted reviews using the AGREE II tool. The panel of experts agreed within the 6 AGREE domains. Future implementation of this guideline, translation process, and evaluation tool will impact social change through the empowerment of the clinical staff, patients, and caregivers to provide the best pain control and comfort at end of life, a vulnerable time for all patients.