Participação plurissocial para aumentar a inclusão e a assertividade nas tomadas de decisão em saúde relacionadas a tratamentos da osteoporose / Pluri-social participation to increase inclusion and assertiveness in health decision-making related to osteoporosis treatments

Embora as fraturas por fragilidade sejam importantes detratoras de qualidade de vida relacionada à saúde, aumentando a morbimortalidade e acarretando alto impacto clínico, psicossocial e econômico, elas são pouco valorizadas e negligenciadas por médicos e até mesmo por pacientes. Além disso, os critérios de priorização para avaliação de novas tecnologias, em geral, não consideram critérios além dos financeiros para uma tomada de decisão mais inclusiva e assertiva para o tratamento da população de mais alto risco de fratura. Assim, este artigo visa revisitar alguns diferentes pontos de vista e trazer uma reflexão sobre critérios e prioridades na osteoporose. Para isso, foi considerada a perspectiva de múltiplos atores no processo de tomada de decisão em saúde, bem como analisadas as falhas na atenção a uma doença de alta prevalência e que, além do grande impacto econômico gerado para a sociedade, causa repercussões emocionais, incapacidade gerada por fraturas e medo de novas quedas ou pequenos traumas.

Although fragility fractures are important detractors of health-related quality of life, increasing morbidity and mortality and causing a high clinical, psychosocial, and economic impact, they are undervalued and neglected by physicians and even patients. In addition, prioritization criteria for evaluating new technologies, in general, do not consider criteria other than financial ones for a more inclusive and assertive decision-making for the treatment of the population at higher risk of fracture. Thus, this article aims to revisit some different points of view and bring a reflection on criteria and priorities in osteoporosis. For this, the perspective of multiple stakeholders in the health decision-making process was considered, as well as the failures in the care of this highly prevalent disease that, in addition to the great economic impact generated for society, causes emotional repercussions, disability generated by fractures and fear of further falls or minor trauma.

Uma abordagem de Análise de Decisão Multicritérios (MCDA) para identificar e priorizar critérios de tomada de decisão para tratamentos da osteoporose pós-menopausa no Sistema Único de Saúde do Brasil / A Multicriteria Decision Analysis (MCDA) framework to identify and prioritize criteria for guiding decision making for postmenopausal osteoporosis treatment in the Brazilian Public Healthcare System

Objetivo: Identificar os principais critérios e preferências na tomada de decisão em saúde para osteoporose pós-menopausa, por três grupos de stakeholders (n=3, cada): médicos; representantes de pacientes; gestores de saúde. Métodos: Uma estrutura de Análise de Decisão Multicritério (MCDA) foi realizada para gerar priorização entre tecnologias: uma revisão da literatura formou conjuntos de critérios; um painel online validou os critérios selecionados; o método AHP (Analytic Hierarchy Process) atribuiu pesos de importância para cada critério, por consenso. Resultados: Os critérios avaliados foram: eficácia (fraturas clínicas, vertebrais, não vertebrais e de quadril, densidade mineral óssea), segurança (eventos adversos e tolerabilidade), conveniência (adesão e comodidade posológica) e economia (razão de custo-efetividade incremental ­ RCEI, custo por respondedor, impacto orçamentário e custos indiretos). Fraturas clínicas e de quadril apareceram nas primeiras posições para todos os grupos. Para os médicos, fratura de quadril (26,11%) e eventos adversos (14,64%) foram os principais critérios de priorização; para os representantes dos pacientes, fratura clínica (25,09%) e de quadril (22,84%), enquanto critérios econômicos receberam os menores pesos (1,2% a 0,98%), abaixo da comodidade posológica, por exemplo (4%). Gestores públicos priorizaram RCEI (19,44%) e fratura de quadril (16,21%). Conclusões: Os resultados apresentados têm potencial para auxiliar na tomada de decisão e priorização de tratamentos para osteoporose e estão em linha ao observado em estudos de preferência nesta área terapêutica. Embora os pesos finais tenham variado entre os grupos, os desfechos de eficácia que envolvem fraturas foram os critérios priorizados.

Objective: To identify the main criteria and preferences in healthcare decision-making for postmenopausal osteoporosis according to three stakeholder groups (n=3, each): physicians, patient representatives, and public healthcare managers. Methods: A multi-Criteria Decision Analysis framework was performed to generate prioritization rankings between technologies: a literature review formed sets of criteria; an online panel validated the pre-selected criteria; the Analytic Hierarchy Process (AHP) method assigned importance weights to each criterion by consensus. Results: The final weighted average included: efficacy (clinical fractures, new vertebral, non-vertebral, hip fractures, and bone mineral density), safety (clinically significant adverse events and tolerability), convenience (adherence and dosing convenience), and economics (incremental cost-effectiveness ratio ­ ICER, cost per responder, budget impact and indirect costs). New hip and clinical fractures appeared in the top-five positions for all stakeholder groups. For physicians the main criteria were new hip fracture (26.11%) and adverse events (14.64%); similarly, for patient representatives, clinical fracture (25.09%) and new hip fracture (22.84%) were the most important ones, while economic criteria received the lowest weights (1,2% to 0,98%), below dosing convenience, for example (4%). Public healthcare managers prioritized ICER (19.44%) and new hip fractures (16.21%). Conclusions: The presented results have the potential to assist decision-making and treatment prioritization in postmenopausal osteoporosis. Although final weightings varied among stakeholders, efficacy outcomes involving fractures were the priority criteria for all of them. It is possible to observe similar results in previously published studies of preferences in osteoporosis.

Razonamiento clínico en medicina II: hacia una definición integradora / Clinical reasoning in medicine II: Towards an integrating definition

RESUMEN El entendimiento del razonamiento clínico es una necesidad para la investigación, la docencia y la práctica clínica. Los modelos teóricos subyacentes podrían agruparse en tres grandes ejes no excluyentes. El primero es denominado bayesiano informal según su estructura semejante al análisis de probabilidades condicionales. El segundo propone (desde las ciencias cognitivas) un razonamiento dual que es la suma de dos tipos de pensamientos: el tipo 1, rápido e intuitivo y, el tipo 2, hipotético-deductivo. El tercero, el conocimiento intersubjetivo que involucra la interacción del saber del paciente sobre su condición con el del médico, además, de hacer explícito el papel de la emoción. En esta segunda entrega se presenta una revisión narrativa de estas teorías para poder proponer una definición integradora, en la que se presenta al razonamiento clínico como un constructo complejo, iterativo y adaptativo.

SUMMARY Understanding clinical reasoning is a crucial for research, teaching, and daily clinical practice. Theoretical models could be grouped into three main non-exclusive axes. The first describes probability-based thinking, called informal Bayesian, because of its similarity to the conditional probability analysis structure. The second, from the cognitive sciences, describes reasoning as the sum of two types of thinking: type 1 (fast and intuitive) and type 2 (hypothetical-deductive). Finally, the third, intersubjective knowledge, which involves the interaction of the patient's knowledge about his condition with the doctor's knowledge and also makes explicit the role of emotion. In this second part, a narrative review of current theories is presented in order to propose an integrative definition, in which clinical reasoning is presented as a complex, iterative and adaptive construct.

Decision theory for precision therapy of breast cancer.

Correctly estimating the hormone receptor status for estrogen (ER) and progesterone (PGR) is crucial for precision therapy of breast cancer. It is known that conventional diagnostics (immunohistochemistry, IHC) yields a significant rate of wrongly diagnosed receptor status. Here we demonstrate how Dempster Shafer decision Theory (DST) enhances diagnostic precision by adding information from gene expression. We downloaded data of 3753 breast cancer patients from Gene Expression Omnibus. Information from IHC and gene expression was fused according to DST, and the clinical criterion for receptor positivity was re-modelled along DST. Receptor status predicted according to DST was compared with conventional assessment via IHC and gene-expression, and deviations were flagged as questionable. The survival of questionable cases turned out significantly worse (Kaplan Meier p < 1%) than for patients with receptor status confirmed by DST, indicating a substantial enhancement of diagnostic precision via DST. This study is not only relevant for precision medicine but also paves the way for introducing decision theory into OMICS data science.

Combining Model-Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design.

The Bayesian decision-analytic approach to trial design uses prior distributions for treatment effects, updated with likelihoods for proposed trial data. Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric-based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision-theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.

Innovations in applied decision theory for health and safety.

OBJECTIVES: There are established methods for occupational epidemiological cohort analysis, such as proportional hazards regression, that are well suited to aetiological research and yield parameter estimates that allow for succinct communication among academics. However, these methods are not necessarily well suited for evaluation of health impacts of policy choices and communication to decision makers. An informed decision about a policy that impacts health and safety requires a valid estimate of the policy's potential impact. METHODS: We propose methods for data summarisation that may facilitate communication with managers, workers and their advocates. We calculate measures of effect in a framework for competing events, graphically display potential impacts on cause-specific mortality under policy alternatives and contrast these results to estimates obtained using standard Poisson regression methods. Methods are illustrated using a cohort mortality study of 28 546 Ontario uranium miners hired between 1950 and 1996 and followed through 2007. RESULTS: A standard regression analysis yields a positive association between cumulative radon progeny exposure and all-cause mortality (log(RR per 100 WLM)=0.09; SE=0.02). The proposed method yields an estimate of the expected gain in life expectancy (approximately 6 months per worker) and reduction of 261 lung cancer deaths under a policy that eliminated occupational radon progeny exposure. CONCLUSIONS: The proposed method shifts attention from covariate-adjusted risk ratios or rate ratios to estimates of deaths that are avoided or delayed under a potential policy. The approach may help inform decision-making and strengthen the connection of epidemiological approaches to data analysis with developments in decision theory and systems engineering to improve health and safety.

Clinical decision-making at the end of life: a mixed-methods study.

OBJECTIVES: To improve the ability of clinical staff to recognise end of life in hospital inpatients dying as a result of cancer and heart failure, and to generate new hypotheses for further research. METHODS: This mixed-methods study used decision theory as a theoretical basis. It involved a parallel databases-convergent design, incorporating findings from previously published research, with equal priority to study groups and synthesis by triangulation. The individual arms were (1) a retrospective cohort study of 102 patients with cancer and 81 patients with heart failure in an acute trust in the North of England, and(2) a semistructured interview study of 19 healthcare professionals caring for the same patient groups. RESULTS: The synthesis of findings demonstrated areas of agreement, partial agreement, silence and dissonance when comparing the cohort findings with the interview findings. Trajectories of change are identified as associated with poor prognosis in both approaches, but based on different parameters. Management of patients has a significant impact on decision-making. The decision process requires repeated, iterative assessments and may benefit from a multidisciplinary approach. Uncertainty is a defining characteristic of the overall process, and objective parameters only have a limited role in predicting end of life. CONCLUSIONS: The role of uncertainty is important as a trigger for discussions and a defined stage in a patient's illness journey. This is consistent with current approaches to recognising irreversible deterioration in those with serious illness. This study contributes ongoing evidence that these concepts are vital for decision-making.

A Fast Likelihood Method to Reconstruct and Visualize Ancestral Scenarios.

The reconstruction of ancestral scenarios is widely used to study the evolution of characters along phylogenetic trees. One commonly uses the marginal posterior probabilities of the character states, or the joint reconstruction of the most likely scenario. However, marginal reconstructions provide users with state probabilities, which are difficult to interpret and visualize, whereas joint reconstructions select a unique state for every tree node and thus do not reflect the uncertainty of inferences. We propose a simple and fast approach, which is in between these two extremes. We use decision-theory concepts (namely, the Brier score) to associate each node in the tree to a set of likely states. A unique state is predicted in tree regions with low uncertainty, whereas several states are predicted in uncertain regions, typically around the tree root. To visualize the results, we cluster the neighboring nodes associated with the same states and use graph visualization tools. The method is implemented in the PastML program and web server. The results on simulated data demonstrate the accuracy and robustness of the approach. PastML was applied to the phylogeography of Dengue serotype 2 (DENV2), and the evolution of drug resistances in a large HIV data set. These analyses took a few minutes and provided convincing results. PastML retrieved the main transmission routes of human DENV2 and showed the uncertainty of the human-sylvatic DENV2 geographic origin. With HIV, the results show that resistance mutations mostly emerge independently under treatment pressure, but resistance clusters are found, corresponding to transmissions among untreated patients.

The 3 faces of clinical reasoning: Epistemological explorations of disparate error reduction strategies.

There is general consensus that clinical reasoning involves 2 stages: a rapid stage where 1 or more diagnostic hypotheses are advanced and a slower stage where these hypotheses are tested or confirmed. The rapid hypothesis generation stage is considered inaccessible for analysis or observation. Consequently, recent research on clinical reasoning has focused specifically on improving the accuracy of the slower, hypothesis confirmation stage. Three perspectives have developed in this line of research, and each proposes different error reduction strategies for clinical reasoning. This paper considers these 3 perspectives and examines the underlying assumptions. Additionally, this paper reviews the evidence, or lack of, behind each class of error reduction strategies. The first perspective takes an epidemiological stance, appealing to the benefits of incorporating population data and evidence-based medicine in every day clinical reasoning. The second builds on the heuristic and bias research programme, appealing to a special class of dual process reasoning models that theorizes a rapid error prone cognitive process for problem solving with a slower more logical cognitive process capable of correcting those errors. Finally, the third perspective borrows from an exemplar model of categorization that explicitly relates clinical knowledge and experience to diagnostic accuracy.

A Gaussian Approximation Approach for Value of Information Analysis.

Most decisions are associated with uncertainty. Value of information (VOI) analysis quantifies the opportunity loss associated with choosing a suboptimal intervention based on current imperfect information. VOI can inform the value of collecting additional information, resource allocation, research prioritization, and future research designs. However, in practice, VOI remains underused due to many conceptual and computational challenges associated with its application. Expected value of sample information (EVSI) is rooted in Bayesian statistical decision theory and measures the value of information from a finite sample. The past few years have witnessed a dramatic growth in computationally efficient methods to calculate EVSI, including metamodeling. However, little research has been done to simplify the experimental data collection step inherent to all EVSI computations, especially for correlated model parameters. This article proposes a general Gaussian approximation (GA) of the traditional Bayesian updating approach based on the original work by Raiffa and Schlaifer to compute EVSI. The proposed approach uses a single probabilistic sensitivity analysis (PSA) data set and involves 2 steps: 1) a linear metamodel step to compute the EVSI on the preposterior distributions and 2) a GA step to compute the preposterior distribution of the parameters of interest. The proposed approach is efficient and can be applied for a wide range of data collection designs involving multiple non-Gaussian parameters and unbalanced study designs. Our approach is particularly useful when the parameters of an economic evaluation are correlated or interact.

Computation and measurement of cell decision making errors using single cell data.

In this study a new computational method is developed to quantify decision making errors in cells, caused by noise and signaling failures. Analysis of tumor necrosis factor (TNF) signaling pathway which regulates the transcription factor Nuclear Factor κB (NF-κB) using this method identifies two types of incorrect cell decisions called false alarm and miss. These two events represent, respectively, declaring a signal which is not present and missing a signal that does exist. Using single cell experimental data and the developed method, we compute false alarm and miss error probabilities in wild-type cells and provide a formulation which shows how these metrics depend on the signal transduction noise level. We also show that in the presence of abnormalities in a cell, decision making processes can be significantly affected, compared to a wild-type cell, and the method is able to model and measure such effects. In the TNF-NF-κB pathway, the method computes and reveals changes in false alarm and miss probabilities in A20-deficient cells, caused by cell's inability to inhibit TNF-induced NF-κB response. In biological terms, a higher false alarm metric in this abnormal TNF signaling system indicates perceiving more cytokine signals which in fact do not exist at the system input, whereas a higher miss metric indicates that it is highly likely to miss signals that actually exist. Overall, this study demonstrates the ability of the developed method for modeling cell decision making errors under normal and abnormal conditions, and in the presence of transduction noise uncertainty. Compared to the previously reported pathway capacity metric, our results suggest that the introduced decision error metrics characterize signaling failures more accurately. This is mainly because while capacity is a useful metric to study information transmission in signaling pathways, it does not capture the overlap between TNF-induced noisy response curves.

Hospital Regional do Juruá e a política pública de saúde no Acre, no início do século XXI, sob governos hegemonizados pelo Partido dos Trabalhadores / Hospital Regional do Juruá and public health policy in Acre at the beginning of the 21st century under governments hegemonized by the Partido dos Trabalhadores

Introdução A partir da pergunta de partida Que fatores levaram um partido de origem socialista a optar por uma gerência terceirizada na Saúde? procurou-se analisar a parceria de um Órgão Público com o Terceiro Setor, para gerenciar um hospital regional, definindo-se, como objeto, o caso do Hospital Regional do Juruá, Acre, no início do século XXI. Objetivo Analisar as implicações do gerenciamento terceirizado de um hospital público e a política pública de saúde no Acre, no início do século XXI, sob governos hegemonizados pelo Partido dos Trabalhadores. Método estudo de metodologia qualitativa, utilizou um estudo de caso, onde foram realizadas revisão de bibliografia, análise documental e coleta de dados empíricos. A população de referência foi constituída por gestores, trabalhadores e usuários do SUS. Os dados foram obtidos por meio de pesquisa documental e de entrevista com roteiro. O conteúdo das entrevistas foi sistematizado com o auxílio da técnica do Discurso do Sujeito Coletivo. Posteriormente, foi triangulado com os dados oriundos da pesquisa documental. A análise final utilizou a Teoria da Escolha Racional. Resultados As transformações ocorridas no mundo desde a década de 1980 atingiram o PT na sua trajetória e o colocaram diante da escolha de maximizar votos para chegar ao poder, optando por ampliar suas alianças e fazendo uma virada ideológica pragmática. No Acre, a eleição da Frente Popular representou uma ruptura com o sistema político local inaugurando um projeto de Poder de longo prazo. A Saúde Pública foi bastante impactada, resultando num serviço de melhor qualidade, reconhecido pela população. Os governos agiram racionalmente para maximizar o apoio político, tomando decisões eficientemente planejadas para alcançar os fins econômicos e políticos desejados. Dentre essas escolhas, esteve a decisão de firmar parceria com o Terceiro Setor para gerenciar um hospital de referência regional. Conclusões A contradição inicial de um governo do Partido dos Trabalhadores em utilizar o modelo de terceirização para gerir um hospital público foi explicada através das escolhas racionais feitas pelos seus governos diante das alternativas colocadas, analisando-se as várias condições que dificultavam o funcionamento de um hospital numa localidade geograficamente isolada. Entretanto, a lógica da parceria com o Terceiro Setor foi naturalizada, favorecendo a acomodação dos interesses das partes envolvidas, e consolidando-se como permanente

Introduction From the starting question \"What factors led a party of socialist origin to opt for outsourced management in Health?\" sought to analyze the partnership of a Public Organ with the Third Sector, to manage a regional hospital, defining, as object, the case of the Hospital Regional do Juruá , Acre, at the beginning of the 21st century. Objective To analyze the implications of outsourced management of a public hospital and public health policy in Acre at the beginning of the 21st century under governments hegemonized by the Partido dos Trabalhadores. Method Study of qualitative methodology, used a case study, where they were carried out review of bibliography, documentary analysis and empirical data collection. The reference population was made up of SUS managers, workers and users. The data were obtained through documentary research and interview with script. The content of the interviews was systematized with the help of the Collective Subject Discourse technique. Subsequently, it was triangulated with data from documentary research. The final analysis used the Rational Choice Theory. Results The transformations that have occurred in the world since the 1980s have reached the PT in its trajectory and have placed it before the choice of maximizing votes to reach power, opting to broaden its alliances and making a pragmatic ideological turn. In Acre, the Popular Front election represented a break with the local political system inaugurating a long-term power project. Public Health was very impacted, resulting in a better quality service, recognized by the population. Governments acted rationally to maximize political support by making efficiently planned decisions to achieve the desired economic and political ends. Among these choices was the decision to establish a partnership with the Third Sector to manage a regional reference hospital. Conclusions The initial contradiction of a Partido dos Trabalhadores government in using the outsourcing model to run a public hospital was explained through the rational choices made by its governments in the face of the alternatives placed by analyzing the various conditions that hindered the operation of a hospital in a Locally geographically isolated. However, the logic of the partnership with the Third Sector was naturalized, favoring the accommodation of the interests of the parties involved, and consolidating as permanent

Tomada de decisão em (bio)ética clínica: abordagens contemporâneas / Decision-making in clinical (bio)ethics: contemporary approaches / Toma de decisiones en (bio)ética clínica: enfoques contemporáneos

Tomar decisões diante de problema moral na prática clínica tornou-se aspecto de suma importância para todos os profissionais envolvidos no cuidado da saúde. Este estudo considera esse contexto de incertezas, em que se discutem reais benefícios e acesso às novas tecnologias em saúde, e parte do pressuposto que qualquer deliberação em (bio)ética clínica resulta do princípio de que respeito pelo ser humano é indispensável para o agir correto. Este artigo tem como proposta 1) identificar na literatura alguns dos aspectos que transpassam e angustiam os profissionais de saúde e/ou pesquisadores na prática clínica, e 2) apresentar sucintamente reflexões ou abordagens correlacionadas ao processo decisório em (bio)ética clínica em relação aos casos identificados. O caminho percorrido neste estudo diz respeito à revisão da literatura científica com estratégia de busca definida.

Taking decisions in the face of moral problems in clinical practice has become a very important aspect for all professionals involved in health care. This study considers this context of uncertainty, in which there are discussions regarding the real benefits and access to new technologies in health, and assumes that any resolution in clinical (bio)ethics results from the principle that respect for the human being is indispensable for correct actions. This article aims to 1) identify in literature some of the aspects that cause anguish in health care professionals and/or researchers in clinical practice, and 2) briefly present the reflections or correlated approaches used in the decision-making process in clinical (bio)ethics of identified cases. This study’s process refers to a review of scientific literature with a defined search strategy.

Tomar decisiones frente a un problema moral en la práctica clínica se ha tornado un aspecto de suma importancia para todos los profesionales involucrados en la atención de la salud. El presente estudio considera este contexto de incertidumbre en el que se discuten los beneficios reales y el acceso a las nuevas tecnologías en materia de salud, y parte del supuesto de que cualquier deliberación en (bio)ética clínica se desprende del principio de que el respeto por el ser humano es indispensable para actuar correctamente. Este artículo se propone: 1) identificar en la literatura algunos de los aspectos que atraviesan y generan angustia a profesionales de la salud y/o investigadores en la práctica clínica, y 2) presentar brevemente las reflexiones o enfoques relacionados al proceso decisorio en (bio)ética clínica en relación a los casos identificados. El camino recorrido en este estudio da cuenta de una revisión de la literatura científica con una estrategia de búsqueda definida.

Restaging oesophageal cancer after neoadjuvant therapy with (18)F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery.

OBJECTIVES: It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk. METHODS: This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by (18)F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014). RESULTS: Three hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91 %) and PET-CT in 17 (6.07 %). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1 %). PET-CT was more sensitive than CT (p = 0.005, McNemar's test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0 %; both risk factors), medium (22.4 %; either), and low risk (3.87 %; neither) groups (p < 0.001). Decision theory supported restaging PET-CT. CONCLUSIONS: PET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply. KEY POINTS: • Restaging (18) F-FDG-PET-CT after neoadjuvant chemotherapy identifies metastases in 6 % of patients • Restaging (18) F-FDG-PET-CT is more sensitive than CT for detecting interval progression • Despite this, at surgery 10 % of patients had unsuspected incurable disease • New concepts (FDG-avid nodal stage and response) plus tumour impassability stratify risk • Higher risk (if not all) patients may benefit from additional restaging modalities.

A decision-theoretic phase I-II design for ordinal outcomes in two cycles.

This paper is motivated by a phase I-II clinical trial of a targeted agent for advanced solid tumors. We study a stylized version of this trial with the goal to determine optimal actions in each of two cycles of therapy. A design is presented that generalizes the decision-theoretic two-cycle design of Lee and others (2015. Bayesian dose-finding in two treatment cycles based on the joint utility of efficacy and toxicity. Journal of the American Statistical Association, to appear) to accommodate ordinal outcomes. Backward induction is used to jointly optimize the actions taken for each patient in each of the two cycles, with the second action accounting for the patient's cycle 1 dose and outcomes. A simulation study shows that simpler designs obtained by dichotomizing the ordinal outcomes either perform very similarly to the proposed design, or have much worse performance in some scenarios. We also compare the proposed design with the simpler approaches of optimizing the doses in each cycle separately, or ignoring the distinction between cycles 1 and 2.

Pragmatic staging of oesophageal cancer using decision theory involving selective endoscopic ultrasonography, PET and laparoscopy.

BACKGROUND: Following CT, guidelines for staging oesophageal and gastro-oesophageal junction (GOJ) cancer recommend endoscopic ultrasonography (EUS), PET-CT and laparoscopy for T3-T4 GOJ tumours. These recommendations are based on generic utilities, but it is unclear whether the test risk outweighs the potential benefit for some patients. This study sought to quantify investigation risks, benefits and utilities, in order to develop pragmatic, personalized staging recommendations. METHODS: All patients with a histological diagnosis of oesophageal or GOJ cancer staged between May 2006 and July 2013 comprised a development set; those staged from July 2013 to July 2014 formed the prospective validation set. Probability thresholds of altering management were calculated and predictive factors identified. Algorithms and models (decision tree analysis, logistic regression, artificial neural networks) were validated internally and independently. RESULTS: Some 953 patients were staged following CT, by [(18) F]fluorodeoxyglucose PET-CT (918), EUS (798) and laparoscopy (458). Of these patients, 829 comprised the development set (800 PET-CT, 698 EUS, 397 laparoscopy) and 124 the validation set (118 PET-CT, 100 EUS, 61 laparoscopy). EUS utility in the 71.8 per cent of patients with T2-T4a disease on CT was minimal (0.4 per cent), its risk exceeding benefit. EUS was moderately accurate for pT1 N0 disease. A number of factors predicted metastases on PET-CT and laparoscopy, although none could inform an algorithm. PET-CT altered management in 23.0 per cent, and laparoscopy in 7.1 per cent, including those with T2 and distal oesophageal tumours. CONCLUSION: Although EUS provided additional information on T and N category, its risk outweighed potential benefit in patients with T2-T4a disease on CT. Laparoscopy seemed justified for distal oesophageal tumours of T2 or greater.

Anterior temporal lobectomy compared with laser thermal hippocampectomy for mesial temporal epilepsy: A threshold analysis study.

PURPOSE: Anterior Temporal Lobectomy (ATL) is the gold standard surgical treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks associated with invasiveness, including cognitive and visual deficits and potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a new procedure that offers a less invasive alternative to the standard open approach. In this decision analysis, we determine the seizure freedom rate at which LTH would be equivalent to ATL. METHODS: MEDLINE searches were performed for studies of ATL from 1995 to 2014. Using complication and success rates from the literature, we constructed a decision analysis model for treatment with ATL and LTH. Quality-adjusted life years (QALYs) were derived from examining patient preferences in similar clinical conditions. LTH data were obtained from a preliminary multicenter study report following patients for 6-12 months. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. RESULTS: 350 studies involving 25,144 cases of ATL were included. Outcomes of LTH were taken from a recently presented multicenter series of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668 QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities of seizure control and late morbidity of LTH are most likely to affect outcomes compared to ATL. We calculated that LTH would need to stop disabling seizures (Engel class I) in at least 43% of cases and have fewer than 40% late mortality/morbidity to result in quality of life at least as good as that after ATL. CONCLUSIONS: This decision analysis based on early follow-up data suggests LTH has similar utility to ATL. These early data support LTH as a potentially comparable less invasive alternative to ATL in refractory TLE. LTH utility may remain comparable to ATL even if long-term seizure control is less than that of ATL. Larger prospective studies with long-term follow up will be needed to validate the true role of LTH in the refractory epilepsy patient population.

Classification in two-stage screening.

Decision theory is applied to the problem of setting thresholds in medical screening when it is organised in two stages. In the first stage that involves a less expensive procedure that can be applied on a mass scale, an individual is classified as a negative or a likely positive. In the second stage, the likely positives are subjected to another test that classifies them as (definite) positives or negatives. The second-stage test is more accurate, but also more expensive and more involved, and so there are incentives to restrict its application. Robustness of the method with respect to the parameters, some of which have to be set by elicitation, is assessed by sensitivity analysis.

Testing a Preliminary Live with Love Conceptual Framework for cancer couple dyads: A mixed-methods study.

PURPOSE: The purpose of this study was to test the previous proposed Preliminary Live with Love Conceptual Framework (P-LLCF) that focuses on spousal caregiver-patient couples in their journey of coping with cancer as dyads. METHODS: A mixed-methods study that included qualitative and quantitative approaches was conducted. Methods of concept and theory analysis, and structural equation modeling (SEM) were applied in testing the P-LLCF. RESULTS: In the qualitative approach in testing the concepts included in the P-LLCF, a comparison was made between the P-LLCF with a preliminary conceptual framework derived from focus group interviews among Chinese couples' coping with cancer. The comparison showed that the concepts identified in the P-LLCF are relevant to the phenomenon under scrutiny, and attributes of the concepts are consistent with those identified among Chinese cancer couple dyads. In the quantitative study, 117 cancer couples were recruited. The findings showed that inter-relationships exist among the components included in the P-LLCF: event situation, dyadic mediators, dyadic appraisal, dyadic coping, and dyadic outcomes. In that the event situation will impact the dyadic outcomes directly or indirectly through Dyadic Mediators. The dyadic mediators, dyadic appraisal, and dyadic coping are interrelated and work together to benefit the dyadic outcomes. CONCLUSIONS: This study provides evidence that supports the interlinked components and the relationship included in the P-LLCF. The findings of this study are important in that they provide healthcare professionals with guidance and directions according to the P-LLCF on how to plan supportive programs for couples coping with cancer.