A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

BACKGROUND: High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, lifeyears, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data

Development and validation of a Medication Adherence Universal Questionnaire: the MAUQ

Abstract Background Different questionnaires assess self-reported medication adherence and others quantify aspects of patients attitudes towards medication, but not together in a single instrument. Gathering these two aspects in a single instrument could reduce patients survey burden. Aim The aim of this study was to develop the Medication Adherence Universal Questionnaire (MAUQ) using the Maastricht Utrecht Adherence in Hypertension short version (MUAH-16) factorial structure as the hypothesized model. Method A multistep process started with the modification of the MUAH-16 to obtain the MAUQ. Patients using at least one antihypertensive medicine were recruited. The two questionnaires, the MUAH-16 and MAUQ, were applied. A confirmatory factor analysis (CFA) was performed using the initial MUAH-16 s-order 4-factor model. An additional bifactor model with four uncorrelated factors and an overall score was tested. The comparative fit index (CFI), root mean square error of approximation (RMSEA) with confidence intervals (CIs), and standardized root mean squared residual (SRMR) were used to assess both models. Results A sample of 300 hypertensive patients completed the instruments. The CFA with the second-order 4-factor solution resulted in similar results for the MUAH-16 and MAUQ: CFIs of 0.934 and 0.930, RMSEAs of 0.043 [CI 0.0300.056] and 0.045 [CI 0.0310.057] and SRMRs of 0.060 and 0.061, respectively. The CFA with the bifactor model showed slightly better results for both the MUAH-16 and MAUQ: CFIs of 0.974 and 0.976, RMSEAs of 0.030 [CI 0.0050.046] and 0.028 [CI 0.0010.044], and SRMRs of 0.043 and 0.044, respectively. Conclusion CFA demonstrated that the MAUQ presented a better fit to both models than the MUAH-16, obtaining a robust universal free instrument to assess medicine-taking behaviour and four medicine beliefs components. </jats:sec

Pros and Against of hormonal contraception

São reconhecidos diversos benefícios da contraceção hormonal em mulheres saudáveis: ciclos regulares, sem hemorragia abundante, sem dismenorreia e sem síndroma pré-menstrual. Mas a contraceção hormonal pode ser utilizada com objetivos terapêuticos específicos: tratamento da síndrome dos ovários poliquísticos, da endometriose, de diversos distúrbios hemorrágicos vaginais da mulher e, com as pílulas contracetivas que associam ao etinilestradiol um progestagénio com atividade antiandrogénica, terapêutica a longo prazo de acne, seborreia, hirsutismo e alopécia. Há ainda evidência científica de que a contraceção hormonal diminui o risco de aparecimento de quistos ou tumores nos ovários ou no endométrio.No entanto, a contraceção hormonal tem também os seus riscos. Sendo estes dependentes da dose, estima-se que nos contracetivos orais modernos, de baixa dosagem, eles sejam bastante menos frequentes e intensos do que nos primórdios da sua comercialização, mas não deixam de manifestar-se. Os mais frequentes estão associados a uma diminuição do bem-estar físico e/ou psicológico da mulher. Há também alguma evidência científica de que os contracetivos hormonais possam estar envolvidos no aparecimento/desenvolvimento de tumores hepáticos benignos, bem como no aumento do risco de litíase biliar. Contudo, os efeitos adversos mais graves são os efeitos cardiovasculares: aumento do risco de doença tromboembólica, aparecimento/agravamento de hipertensão arterial, dislipidémias e intolerância à glicose, e o consequente aumento do risco de doenças cardiovasculares. Por fim, a literatura refere que os contracetivos hormonais aumentam o risco de desenvolvimento de determinadas neoplasias, nomeadamente no colo do útero e na mama.Como em relação a qualquer medicamento, a relação benefício-risco terá sempre de ser tida em conta quando se prescreve contraceção hormonal, devendo o princípio da individualização terapêutica ter por base critérios científicos e clínicos mas também pessoais e socioeconómicos. Também no que se refere à contraceção se deve seguir a medicina baseada na evidência: usar toda a informação científica e disponibilizá-la à mulher para que ela, no contexto biopsicossocial em que se insere, possa tomar uma decisão informada no que se refere à sua fertilidade.Many benefits of the contraceptive pill are recognized in healthy women: regular cycles, without heavy bleeding, without dysmenorrhea and without premenstrual syndrome. But the contraceptive pill can be used for specific therapeutic objectives: treatment of polycystic ovaries, endometriosis, vaginal bleeding disorders and in long term acne, seborrhea, hirsutism and alopecia therapy (contraceptive pills containing ethinyl estradiol and a progestogen with antiandrogenic activity). There is still scientific evidence that the contraceptive pill reduces the risk of appearance of tumors or cysts in the ovary or endometrium.However the contraceptive pill also has its risks. These being dependent on the dose, it is estimated that in modern low-dose oral contraceptives, they are much less frequent and intense than in the early days of their marketing, but do not fail to manifest themselves. The most common are those that lead to a decrease in physical and / or psychological well-being of women. There is also some scientific evidence that hormonal contraceptives may be involved in the onset / development of benign liver tumors as well as increased risk of gallstones. But the most serious adverse effects are cardiovascular effects: increased risk of thromboembolic disease, onset / worsening of hypertension, dyslipidaemia and glucose intolerance, and the consequent increased risk of cardiovascular disease. Finally, the literature refers that hormonal contraceptives increase the risk of developing certain cancers, especially in the cervix and breast.As with any drug, the risk-benefit ratio must always be taken into account when prescribing one contraceptive pill, and the principle of therapeutic individualization should be based on scientific and clinical but also personal and socio-economic criteria. Also in regard to contraception we should follow evidence-based medicine: use all the scientific information and make it available to the woman so that she, in the biopsychosocial context in which it appears, can make an informed decision regarding her fertility

A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity

Anticholinergic burden tools have relevant pharmacological gaps that may explain their limited predictive ability for clinical outcomes. The aim of this study was to provide a universal pharmacological-based list of drugs with their documented affinity for muscarinic receptors. A comprehensive literature review was performed to identify the anticholinergic burden tools. Drugs included in these instruments were searched in four pharmacological databases, and the investigation was supplemented with PubMed. The evidence regarding the potential antagonism of the five muscarinic receptors of each drug was assessed. The proportion of drugs included in the tools with an affinity for muscarinic receptors was evaluated. A universal list of drugs with anticholinergic activity was developed based on their documented affinity for the different subtypes of muscarinic receptors and their ability to cross the blood-brain barrier. A total of 23 tools were identified, including 304 different drugs. Only 48.68%, 47.70%, 48.03%, 43.75%, and 42.76% of the drugs had an affinity to the M1, M2, M3, M4, and M5 receptor, respectively, reported in any pharmacological database. The proportion of drugs with confirmed antagonism varied among the tools (36.8% to 100%). A universal pharmacological-based list of 133 drugs is presented. It should be further validated in different clinical settings. (c) 2023 by the authors

Lamotrigine analysis in blood and brain by high-performance liquid chromatography

A reversed-phase high-performance liquid chromatography assay was developed and validated to determine plasma and brain lamotrigine concentrations allowing pharmacokinetic-pharmacodynamic studies of this new antiepileptic drug in patients and laboratory animals. Lamotrigine and its internal standard were extracted, under alkaline conditions, from plasma and brain homogenate, into ethyl acetate; brain proteins were previously precipitated with trichloroacetic acid. The method was linear between 0.1 and 15.0 mg/l for plasma, with a detection limit of 0.008 mg/l, and between 0.1 and 5.0 mg/l for brain homogenate, with a detection limit of 0.023 mg/l. The method proved to be simple, useful and appropriate, not only for clinical and experimental research, but also for routine monitoring of lamotrigine concentrations in patients.http://www.sciencedirect.com/science/article/B6TG9-42T4DX1-G/1/114ff1c7668d24d37232dc1f255aeb1

Efeito da adesão à terapêutica no estado de saúde do idoso

The prevalence of chronic diseases increases with age, and the constant growth of the overall population makes adherence to therapy a major challenge. A solution to the problem of non-adherence to therapy prescribed by the physician population is the implementation, in community pharmacy, of stock monitoring and pharmacist intervention. We evaluated 54 elderly patients treated with at least 3 drugs with an autonomous life. Adherence to drugs prescription was observed by monitoring the patients, counting of medications not administered and historical progress of the lipid profile, blood glucose, blood pressure and cardiovascular risk in the beginning and end of the study. The purpose of this study was achieved in general, since the pharmaceutical intervention contributed to the adherence to therapy, thereby reducing the impact of risk factors associated with cardiovascular disease, and contribute to the promotion of quality of life for the elderly patients. A prevalência de doenças crónicas aumenta com o envelhecimento, e o constante crescimento do contingente populacional faz da adesão à terapêutica um grande desafio. Uma solução para o problema da não adesão à terapêutica prescrita pelo médico na população é a implementação, na farmácia comunitária, de ações de intervenção e acompanhamento farmacêutico. Foram avaliados 54 idosos medicados com pelo menos 3 medicamentos e que viviam de uma forma autónoma. A adesão à prescrição médica foi observada pelo acompanhamento dos doentes, contagem de medicamentos não administrados e evolução dos resultados do perfil lipídico, glicemia, pressão arterial e risco cardiovascular, no início e fim do estudo. O objetivo deste estudo foi na sua generalidade alcançado, uma vez que a intervenção farmacêutica contribuiu para a adesão à terapêutica, reduzindo deste modo o impacto de fatores de risco associados às doenças cardiovasculares, promovendo a qualidade de vida dos idosos.

Implications of a defined daily dose fixed database for drug utilization research studies: The case of statins in Portugal

Aims Given the discrepancies between PDDs (prescribed daily doses) and DDDs (defined daily doses), we aimed to assess the extent of error in the results of an 18-year population-level study on statin utilization in Portugal. Methods The Portuguese regulatory agency provided data for the period 2000-2018 on statin dispensing (C10AA). The DDDs were gathered from the ATC/DDD database. DDDs were calculated by the DDD year-by-year approach (DDDYEAR) and by the DDD last-year approach (DDDLAST). PDDs were calculated according to the year-by-year approach (PDDYEAR). Statin annual utilization rates per 1000 inhabitants per day were also calculated. Percent errors were calculated for PDDYEAR and DDDYEAR units. Results The DDDYEAR approach revealed decreases in the consumption of atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin in 2009, when their DDD was modified. Conversely, the results from both DDDLAST and PDDYEAR approaches indicated gradual changes in the actual consumption of all statins in Portugal. Before 2009, atorvastatin, pravastatin and simvastatin utilization was greatly overestimated by DDDYEAR/1000 inhabitants/day. The average dose of lovastatin prescribed in the past 18 years (20 mg) was below the assigned DDDs during the study period, varying from 30 mg to 45 mg. Conversely, the PDD for fluvastatin was above the DDD values (ranging from 40 mg in 2000 to 70 mg in 2016). For atorvastatin, pravastatin and simvastatin, national PDDs were above the assigned DDD until the DDD modification in 2009. Conclusions A more dynamic system, based on national and annually updated DDDs, should be able to reduce discrepancies between DDDs and PDDs and the bias in utilization studies

Necessidades reais de implementação de novos serviços farmacêuticos centrados no doente

While new more potent and complex pharmaceutical agents are becoming available, increasing demands on doctors and the health care system, the increase of drug related morbidity and mortality throughout the world and rising costs related with the incorrect use of medicines make it clear that the identification of a practitioner who is available to focus on the management of all of a patient’s medicines would be an important asset to the future of human health. Medicines are precious, but patients need to learn how to use them. It is possible that this will be one of the advantages that the pharmacist, as a medicine specialist, will bring to the health system, i.e. the promotion of the rational use of medicines as laid down in legislation. The correct use of medicines will significantly decrease the negative outcomes of phar- macotherapy, namely untreated health problems, ineffective treatment and unsafe treatment.Pharmaceutical care is a patient-centered philosophy of assistential practice in which the pharmacist, as a health care team member, has responsibilities in patient medication. There are pharmaceutical services that monitor the process of the use of medicines from a preventive standpoint, identifying risk factors and acting within their constraints – dispensing, preventable morbidity indicators, medication review – and there are pharmaceutical services that monitor the outcomes from a reactive standpoint, identifying negative clinical outcomes and acting on their causes – pharmacotherapy follow-up, disease management. The clinical pharmacist will have to develop new competencies in communication, information retrieval, critical analysis, ethical behavior, teamwork and leadership. And, more than ever, the clinical pharmacist will have to be technically competent, which requires solid training in cellular biology, biochemistry, anatomophysiology, physiopathology, pharmacology and pharmacotherapy. The assistential pharmacist will have to learn to systematize and to register its action in each type of service carried out. The main barrier that he will have to overcome will be his own mind. This will not only provide new ways of boosting the professional satisfaction of the clinical pharmacist but will also provide concrete answers to the real situations of patients, who will ultimately receive better care. Novos fármacos mais potentes e complexos, menor disponibilidade de médicos e menor acessibilidade ao serviço de saúde, morbilidade e mortalidade relacionadas com medicamentos sempre a aumentar e custos significativos relacionados com o uso incorrecto dos medicamentos justificam plenamente um profissional focado apenas na gestão de toda a medicação do doente. O medicamento é um bem precioso, mas os doentes necessitam de aprender a utilizá-lo. Porventura será essa uma das mais-valias que o farmacêutico, enquanto especialista do medicamento, poderá aportar actualmente ao sistema de saúde: a promoção do uso racional do medicamento, tal como inscrito na legislação em vigor. Uma correcta utilização do medicamento diminuirá significativamente os resultados negativos da farmacoterapia, que se podem manifestar quer como problema de saúde não tratado quer como inefectividade ou insegurança. Os cuidados farmacêuticos correspondem a uma filosofia de actuação assistencial centrada no doente em que o farmacêutico, integrado na equipa de saúde, assume as suas responsabilidades perante a medicação. Concretiza-se em serviços farmacêuticos que, numa atitude preventiva, identificam e actuam sobre factores de risco existentes durante o processo de uso dos medicamentos – dispensa farmacêutica, indicadores de morbilidade prevenível, revisão da medicação – e em serviços que, numa atitude reactiva, identificam resultados negativos e actuam sobre as suas causas – acompanhamento farmacoterapêutico, gestão da doença. O farmacêutico clínico terá de desenvolver novas competências: comunicação, busca de informação, sentido crítico, comportamento ético, trabalho em equipa, liderança. E terá, mais do que nunca, de ser tecnicamente competente: sólida formação em biologia celular, bioquímica, anatomofisiologia, fisiopatologia, farmacologia e farmacoterapia. Terá ainda de aprender a sistematizar e a registar a sua actuação consoante o tipo de serviço prestado. A principal barreira a vencer será a da sua própria mentalidade. Estes não serão apenas novos caminhos de realização profissional: serão respostas concretas a situações reais dos doentes, que desta forma serão melhor cuidados.

Contribution of Different Patient Information Sources to Create the Best Possible Medication History

Introduction: Obtaining the best possible medication history is the crucial step in medication reconciliation. Our aim was to evaluate the potential contributions of the main data sources available - patient/caregiver, hospital medical records, and shared electronic health records - to obtain an accurate 'best possible medication history'. Material and Methods: An observational cross-sectional study was conducted. Adult patients taking at least one medicine were included. Patient interview was performed upon admission and this information was reconciled with hospital medical records and shared electronic health records, assessed retrospectively. Concordance between sources was assessed. In the shared electronic health records, information was collected for four time-periods: the preceding three, six, nine and 12-months. The proportion of omitted data between time-periods was analysed. Results: A total of 148 patients were admitted, with a mean age of 54.6 +/- 16.3 years. A total of 1639 medicines were retrieved. Only 29% were collected simultaneously in the three sources of information, 40% were only obtained in shared electronic health records and only 5% were obtained exclusively from patients. The total number of medicines gathered in shared electronic health records considering the different time frames were 778 (three-months), 1397 (six-months), 1748 (nine-months), and 1933 (12-months). Discussion: The use of shared electronic health records provides data that were omitted in the other data sources available and retrieving the information at six months is the most efficient procedure to establish the basis of the best possible medication history. Conclusion: Shared electronic health records should be the preferred source of information to supplement the patient or caregiver interview in order to increase the accuracy of best possible medication history of the patient, particularly if collected within the prior six months

Results of a school-based asthma assessment from the upKids questionnaire validation study

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