Decision analytic models, sensitivity analysis and value of information in economic evaluations in health care

Economic evaluations of health care technologies are now commonly carried out to assess the economic value of new pharmaceuticals, medical devices and procedures. The aim of health economic evaluations is to measure, value and compare the costs and benefits of different health care interventions. To date, cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) are the two types of economic evaluations that are applied in the vast majority of economic evaluation studies. Cost-effectiveness estimates in CEAs and CUAs can either be derived from data collected alongside a randomized controlled trial or by means of decision analytic modelling. In situations where evidence from a trial is (e.g. short time horizon of the trial; small sample size), decision analytic modelling provides a structure within which evidence from a range of sources can be directed at a specific decision problem for a defined population and context. Decision analytic models use mathematical relationships to define a series of possible consequences. Based on the inputs of the model, the likelihood of each consequence is expressed in terms of probabilities. It is thus possible to calculate the expected costs and expected outcome for different interventions analyzed in the model. In the first study the cost-effectiveness of extended prophylaxis with fondaparinux of one month versus one week in patients undergoing hip fracture surgery and total hip replacement was analysed. The analysis was based on a decision tree, using a time horizon of 30 days and 5 years. In this CEA the health effect was measured in life-years gained. Depending on the patient population and the time horizon, the extended prophylaxis with fondaparinux was found to be cost-effective or cost-saving. In the second study the cost-effectiveness of risedronate was examined for Swiss osteoporotic women. In this study we developed a time-dependent Markov model to examine the cost-effectiveness of risedronate for women who start a 5 year risedronate therapy between 60 and 90 years of age. This CUA was carried out from a Swiss health care perspective. For osteoporotic women or women with severe osteoporosis we found that risedronate treatment is cost-effective. As expected, the cost-effectiveness estimate is influenced by the patients’ age and disease severity. Two chapters of this thesis are based on a cost-utility analysis of 2 drug-eluting stents (the sirolimus- and the paclitaxel-eluting stent; DES) compared to bare metal stents (BMS). Although DES are now used for several years, concerns remain about their long term safety. Given the threefold higher acquisition costs, it was unclear whether DES are cost-effective when compared to BMS. Based on clinical data with 3-year follow-up we developed a Markov CUA model to shed light on this question. Both DES under analysis were found to not be cost-effective from a US Medicare payer’s perspective. In a further study the decision uncertainty was examined in full depth. With expected value of perfect information (EVPI) analysis total decision uncertainty was assessed. EVPI provides the value a rational decision maker should be willing to spend in order to acquire perfect information. Through expected value of partial perfect information analysis the contribution of groups of parameters towards total decision uncertainty was examined. The uncertainty in the cost-effectiveness estimate is largely driven by the uncertainty in the clinical model input parameters. More precise clinical parameter estimates could be derived from a future clinical trial. To assess the value of such a trial, analysis of expected value of sample information was performed. Although the value of a future trial would be enormous, we show diminishing marginal returns and a linear increase in the costs of the future trial per additional patient enrolled into the trial for sample sizes larger than 2000 patients. The optimal sample size was estimated to be 4700 patients for a 3 year time horizon. To conclude, decision analytic models have a range of uses and are thus an important and powerful tool for economic evaluations in health care. Decision analytic models that incorporate probabilistic sensitivity analysis and closely related expected value of perfect information analysis are best suited to provide decision makers not only with a point estimate for the cost-effectiveness estimate but to quantify in addition decision uncertainty and the value of future research

Perioperative Care

Perioperative care practices worldwide are in the midst of a seeing change with the implementation of multidisciplinary processes that improve surgical outcomes through (1) better patient education, engagement, and participation; (2) enhanced pre-operative, intra-operative, and post-operative care bundles; and (3) interactive audit programs that provide feedback to the surgical team. These improved outcomes include reductions in the frequency and severity of complications and improved throughput, which ultimately reduce operative stress. Practices in theatre as well as ward are becoming more collaborative and evidence-driven.This book is best utilized by perioperative care team members engaged in quality improvement, collaborative practice, and application of innovations in surgical care

Risk Prediction and New Prophylaxis Strategies for Thromboembolism in Cancer

Thromboembolism is a compelling challenge in cancer care because of its life-threatening nature as well as its impact on specific treatments. Current guidelines do not generally recommend antithrombotic prophylaxis, except in selected categories of patients at high risk of thrombosis. Accordingly, several clinical decision models have been developed to guide the oncologist in thromboembolic risk assessment and targeted prophylaxis. Low-molecular-weight heparins (LMWH) are currently considered as the standard approach in clinical practice guidelines, but recent randomized controlled trials (RCT) indicate that direct oral anticoagulants (DOACs) are effective for the treatment/prophylaxis of cancer-associated thromboembolism. However, many unanswered questions remain on the efficacy and safety of anticoagulants in selected cancer subgroups, and in primary and secondary prevention settings, where anticoagulation needs to be balanced on the risk of bleeding complications. Presently, patient selection remains the main challenge. Improvement in existing VTE risk models or the construction of alternative risk assessment tools are needed in order to ameliorate the risk stratification of cancer patients. This reprint will cover the current clinical evidence supporting the standard of care and emerging treatment/prophylactic options for cancer-associated thromboembolism during both active treatment and simultaneous/palliative care. Tailored approaches based on the use of individualized factors to stratify the thrombotic/bleeding risk in each individual patient are discussed

Patients’ and health professionals’ experience with home parenteral therapy

A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Background: The literature review showed a lack of investigation into the patients’ preparation and training on the use of injectable medications out of the hospital setting, its impact on their experience with therapy, and their health outcomes. There is some evidence that the patients might achieve competence with their home parenteral therapy, but they might not achieve confidence. Providing continuous access to advice can boost confidence, but the information needs of patients are often not met. Poor communication can leave patients lacking the knowledge and confidence needed to be competent collaborators in their own care, and affect their perceptions of the service, even when they have positive health outcomes. Aim: This thesis aimed to explore the patients’ and healthcare professionals’ (HCPs) experience regarding home parenteral therapy (HPT), including challenges and opportunities for future homecare services improvements and training standardisation within the UK. Methods and design: This was a mixed method study, which included a clinical audit, qualitative patient interviews regarding their experiences with training prior to commencing HPT, followed by patient and HCP surveys, then finally the development of an example education pathway. Results: A clinical audit of records of patients discharged on extended injectable anticoagulants therapy confirmed that the training on self-injecting and the continuation of treatment post-discharge was not well documented or managed on discharge. The assessment of self-injecting technique and cognitive ability to self-care and manage injectables post-discharge, was also not documented, nor communicated effectively to the primary care team (97.8% of patients had no evidence in their discharge summaries that checks were made to ensure the person discharged was able to use their injectable therapy correctly). A cross-sectional survey-based study was then conducted among 110 consented patients (out of 640 approached), who were identified to be on HPT for various medical conditions, as well as 39 HCPs involved with HPT in a UK hospital NHS Trust. This was to explore their knowledge, experience, perceptions, and opinions regarding the training received related to HPT, and to understand the instruments used for starting patients on HPT. Findings show significant differences in opinions and perceptions on HPT and associated training between these two groups. A qualitative study was then conducted using a semi-structured phone interview with 45 consented patients. Data were explored using an inductive thematic analysis approach to identify key themes relating to patients’ experiences and perceptions of the strengths and challenges of HPT. Patients described various strengths and positive experiences with HPT, while also identifying several challenges they were facing. Feedback was collected about the produced patient educational material. Conclusion: The qualitative information gathered from the clinical audit and patient interviews as well as the qualitative and quantitative data from the questionnaire survey of patients and HCPs were used to create a training package concept and to suggest strategies for improving homecare service in the UK

Experiência Profissionalizante na vertente de Farmácia Comunitária, Hospitalar e Investigação

The present training report was developed to obtain the integrated master’s degree in pharmaceutical sciences. It is subdivided in three chapters that address the three main activities enclosed in the curricular unit “Internship” of the Integrated Master in Pharmaceutical Sciences. The first chapter detailed the laboratorial research component, developed at the Health Sciences Research Center from University of Beira Interior in the area of pharmaceutical chemistry. The ubiquitin proteasome system has been defined as potential target in the treatment of a range of clinical conditions, such as inflammation, neurodegenerative diseases and cancer, particularly, haematological malignancies. A variety of chemical synthesized and natural products have exhibited proteasome inhibitory activity from which three were approved for use in multiple myeloma treatment. 2-Thioxoimidazolidin-4-one arylaldehyde derivatives were described as novel noncovalent proteasome inhibitors in a recent study. Considering the structural similarity of thiobarbituric acid and 2-thioxoimidazolidin-4-one systems, 5-substituted (thio)barbiturate derivatives where designed and efficiently synthesized in this work as a potential novel class of proteasome inhibitors with anticancer interest. In this context, several barbiturate derivatives demonstrated promising antiproliferative effects in different cancer cell lines. Stability study of the 5-benzilidene(thio)barbiturates derivatives in solution was performed and led to the exclusion of 5-benzilidene thiobarbiturates due to their instability. Then, a xanthine oxidase and proteasome inhibition assay were performed. None of the compounds showed relevant inhibition of xanthine oxidase enzyme. However, 5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]barbiturate, 9b, showed interesting inhibitory activity in the proteasome inhibition assay. Cytotoxicity of the assayed compounds was evaluated by the MTT assay in healthy (NHDF) and antiproliferative effect of 9b in cancer cell lines (Caco-2 and PC-3) was assessed and compared with the effect of bortezomib, an approved proteasome inhibitor. Although 9b showed cytotoxicity against healthy and cancer cell lines, it was less potent than bortezomib. The second chapter describes the activities accomplished during the internship in Community Pharmacy that took place in the Pharmacy Holon Covilhã under the supervision of Dr. Patrícia Pais. It is divided to present generally the operations performed at the pharmacy, the legislation that regulates the sector, and the tasks and activities perform. The third chapter describes the hospital pharmacy internship at The Barts Heart Centre in St Bartholomew's Hospital in London, UK that was guided by my main supervisor and contact person, Paul Wright, the Lead Cardiac Pharmacist at Barts. It is organized based on the activity I observed or performed myself. It is divided into four main subchapters, The Barts Heart Centre, Oncology, Clinical trials, and Dispensary.O presente relatório de estágio foi elaborado com o objectivo de obter o grau de Mestre em Ciências Farmacêuticas. Encontra-se subdividida em três capítulos que abordam cada um dos períodos de aprendizagem inseridos na unidade curricular “Estágio” do Mestrado Integrado em Ciências Farmacêuticas. No primeiro capítulo é descrito todo o trabalho realizado no âmbito da área de investigação desenvolvida no Centro de Investigação em Ciências da Saúde da Universidade da Beira Interior, na área da química farmacêutica, sendo este intitulado “Synthesis and evaluation of 5-substituted (thio)barbiturates as proteasomal inhibitors for cancer therapy”. O sistema ubiquitina-proteassoma foi definido como um potencial alvo terapêutico no tratamento de uma série de condições clínicas, tais como inflamação, doenças neurodegenerativas e cancro, particularmente, malignidades hematológicas. Uma variedade de produtos sintéticos e naturais têm sido associados a atividade inibitória do proteassoma, dos quais três compostos, bortezomib, carfilzomib, e ixazomib foram aprovados para uso clínico no tratamento do mieloma múltiplo. Os derivados de arilaldeídos de 2-tioxoimidazolidin-4-ona foram descritos como novos inibidores não covalentes de proteassoma num estudo recente. Face a isso, e considerando a similaridade estrutural dos últimos com os ácidos (tio)barbituricos, hipotetizou-se que derivados 5-substituídos de ácidos (tio)barbitúricos também poderiam ter atividade inibitória do proteassoma. Neste contexto, é também conhecido que vários derivados de barbituratos demonstraram efeitos antiproliferativos promissores em diferentes linhas celulares de cancro. No presente trabalho, foram desenvolvidos varios derivados 5-benzilideno(tio)barbitúricos utilizando como precursores ácidos (tio)barbitúricos e benzaldeídos e água como solvente. Os compostos obtidos foram devidamente caracterizados por determinação dos seus pontos de fusão, e espectroscopia de ressonância magnética nuclear de protão e carbono-13. Verificou-se, durante o estudo, a degreadação dos derivados 5-benzilideno tiobarbitúricos e a formação de bis-(tio)barbiturates em soluções aquosas, levando à exclusão destes compostos da avaliação biológica. Assim, tentou-se sintetizar seletivamente os bis-(tio)barbiturates puros, embora sem sucesso. Alternativamente, realizou-se a redução da dupla ligação exocíclica de 5-benzilidenotiobarbituratos como uma tentativa de aumentar a estabilidade dos compostos sintetizados. Os compostos obtidos foram incluídos nos estudos biológicos. Nos estudos da avaliação biológica foram incluídos os derivados 5-benzilidenobarbitúricos e os 5-benzyl(thio)barbituratos, determinado-se a sua atividade como inibidores do proteassoma e da xantina oxidase, tendo sido também analisando os seus efeitos citotóxicos em linhas celulares saudáveis (NHDF) e cancerígenas (Caco-2 e PC-3). A atividade inibitória do proteasoma dos compostos foi determinada mediante o bioluminescent Proteasome-Glo™ Assay. Num screening inicial, incubaram-se os compostos com a enzima em duas concentrações (10 e 100 µM), tendo sido utilizado o bortezomib como controlo positivo. Para o 5-[1-[2-(4-nitrofenil)hidrazinil]etilideno]-barbiturato 9b, composto que demonstrou a melhor atividade inibitória, procedeu-se a ensaio posterior para determinar a curva concentração-resposta. Os valores de IC50 foram calculados por um ajuste sigmoidal dos resultados obtidos, considerando-se um intervalo de confiança de 95%. Adicionalmente, os compostos foram avaliados quanto à capacidade para inibir a xantina oxidase, não se verificando atividade inibitória da mesma. A similaridade estrutural de 9b e bortezomib foi verificada visualmente, sendo realizados estudos in silico de superposição bidimensional e tridimensional. Os estudos de viabilidade celular foram realizados em fibroblastos normais da derme humana em células de cancro da próstata, e em células de cancro de cólon. Num screening inicial, as células de NHDF foram expostas aos compostos, em concentração de 10 e 100 µM durante 72 horas, tendo sido utilizado o 5-fluorouracilo como controlo positivo. A determinação da proliferação celular foi realizada mediante o ensaio do brometo de [3-(4,5-dimetiltiazol-2-yl)-2,5-difenil tetrazólio]. Para o composto 9b, que apresentou a maior atividade inibitória no ensaio do proteassoma e para bortezomib, efectuaram-se estudos de concentração-resposta. Para tal, os compostos foram incubados com as células, em seis concentrações distintas de cada composto no mesmo período de 72 horas, e os valores de IC50 foram calculados por um ajuste sigmoidal, considerando-se um intervalo de confiança de 95%. Adicionalmente, as células PC-3 e Caco-2 foram expostas a 9b e a bortezomib em diferentes concentrações, igualmente durante um período de 72 h. O composto 9b demonstrou citotoxicidade nas linhas celulares saudáveis e cancerígenas mas, contudo, esta foi inferior à citotoxicidade apresentada pelo bortezomibe. Como trabalho futuro, propõe-se estudos de viabilidade celular linha celular Jurkat, linha de células T leucémicas. Adicionalmente, propõe-se realizar estudos do docking molecular para prever o modo de ligação e afinidade de ligação do 9b com o proteassoma. Por outro lado, será igualmente importante sintesar mais derivados destes compostos, variando os substituintes no seu esqueleto molecular de modo a otimizar os resultados biológicos obtidos. O segundo capítulo é dedicado ao estágio em Farmácia Comunitária orientado pela Dr.ª Patrícia Pais e realizado na Farmácia Holon Covilhã. O terceiro capítulo refere-se ao estágio em Farmácia Hospitalar, que foi realizado no Barts Heart Centre, no Hospital St Bartholomew, em Londres, Reino Unido orientado pelo Dr.Paul Wright, Lead Cardiac Pharmacist em Barts Health NHS Trust. Em ambos os relatórios são abordados as atividades desenvolvidas, os conhecimentos adquiridos ao longo dos meus estágios em farmácia comunitária e em farmácia hospitalar

2022 - The Third Annual Fall Symposium of Student Scholars

The full program book from the Fall 2022 Symposium of Student Scholars, held on November 17, 2022. Includes abstracts from the presentations and posters.https://digitalcommons.kennesaw.edu/sssprograms/1026/thumbnail.jp

Textbook of Patient Safety and Clinical Risk Management

Implementing safety practices in healthcare saves lives and improves the quality of care: it is therefore vital to apply good clinical practices, such as the WHO surgical checklist, to adopt the most appropriate measures for the prevention of assistance-related risks, and to identify the potential ones using tools such as reporting & learning systems. The culture of safety in the care environment and of human factors influencing it should be developed from the beginning of medical studies and in the first years of professional practice, in order to have the maximum impact on clinicians' and nurses' behavior. Medical errors tend to vary with the level of proficiency and experience, and this must be taken into account in adverse events prevention. Human factors assume a decisive importance in resilient organizations, and an understanding of risk control and containment is fundamental for all medical and surgical specialties. This open access book offers recommendations and examples of how to improve patient safety by changing practices, introducing organizational and technological innovations, and creating effective, patient-centered, timely, efficient, and equitable care systems, in order to spread the quality and patient safety culture among the new generation of healthcare professionals, and is intended for residents and young professionals in different clinical specialties

Outcomes in varicose vein disease

Introduction Varicose veins are a common problem with 25-50% of the population symptomatically affected, and chronic venous disease leads to significant impairments in quality of life with substantial health system cost implications. Significant variability exists in the symptoms suffered by patients, the treatment offered and the outcomes achieved. Identification of the optimal treatment pathways for patients remains difficult. Aims i. To ascertain primary care disease knowledge. ii. To assess what affects treatment and identify which patients benefit most. iii. To generate a predictive model of varicose vein outcomes. iv. To assess the impact of altering treatment of varicosities in the context of endovenous truncal vein ablation v. To investigate the early impact of new technologies Methods i. Two survey studies were completed: ⁃ 21 questions assessing venous disease management pathways was disseminated to General Practitioners. ⁃ 19 questions assessing the management of superficial venous thrombosis and was distributed to General Practitioners and Vascular Surgeons. ii. A cohort of consecutive patients with symptomatic chronic venous disease were assessed and completed quality of life questionnaires pre and postintervention. iii. Uni-variable and multi-variable analysis of patient cohort data to facilitate the creation of generalised model of venous treatment outcomes iv. A randomised clinical trial assessing the timing of varicosity avulsion in the context of local anaesthetic endovenous truncal ablation. ⁃ Ambulatory Varicosity avUlsion Later or Synchronised (AVULS) trial. v. Assessment of new technologies ⁃ The European Sapheon Closure system Observed ProspectivE (eSCOPE) study a multi-site cohort observational study of cyanoacrylate glue occlusion of truncal vein incompetence ⁃ The VNUS Versus Clarivein for Varicose Veins (VVCVV) multi-centre randomised clinical trial comparing the procedural pain profile of radiofrequency and mechanochemical ablation. Results i. Education outcomes ⁃ 138 responses were received. The management of chronic venous disease in the primary care setting is disparate and knowledge of current techniques is poor, despite extensive guidance. ⁃ 369 responses were received, from 197 vascular specialists and 172 primary care physicians. Superficial thrombophlebitis management is shown to be diverse and does not adhere to recent evidence. ii. 461 patients were recruited. Patients suffering from chronic venous disease suffer from substantial quality of life impairment, including previously under-recognised depressive symptoms. Treatment of the underlying venous condition provides relief from venous symptoms and improves quality of life. ⁃ Patient symptoms and quality of life do not correlate with anatomical vein diameter, however clinical severity scores do. iii. Predictive modelling produces models that account for 30-41% of the variability in post-operative scores for disease specific quality of life tools, generic quality of life tools, and clinical severity scores. iv. The AVULS trial recruited 101 patients. Simultaneous treatment leads to improved clinical outcomes at up to 1 year and early quality of life improvement. Delayed treatment has a significantly increased risk of requiring further treatment (Odds Ratio 27.78, Relative Risk 18.36, p<0.0001). 95% of patients declining randomisation opted for simultaneous treatment. v. New Technology Outcomes ⁃ The eSCOPE study recruited 70 patients in Europe with good technical outcomes. ⁃ The VVCVV trial (ongoing) has recruited 85 patients, with significantly reduced procedural pain found with mechanochemical ablation. Conclusions Varicose veins are a widespread problem with effective treatment that leads to a significant improvement in quality of life. Education and communication between community and hospital-based medicine is lacking. Predictive modelling of varicose vein symptoms remains difficult due to the multifactorial nature of the disease. Simultaneous treatment of varicosities during endovenous truncal ablation produces improved outcomes and is the option of choice for most patients. Early data on new technologies show they provide less painful procedures with similar outcomes as the established modalities.Open Acces