An 'Adaptive Treatment Strategy' for Oral Vancomycin in Patients with the Orphan Disease Primary Sclerosing Cholangitis.

Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized 'adaptive treatment strategy' is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time.

Adaptive resistance to cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB): Microbiological and clinical issues.

Objectives: Determining the best available therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is a challenge. Cefiderocol is an attractive alternative drug effective against many resistance mechanisms in Gram-negative bacteria. However, its place in the treatment of Acinetobacter baumannii infections remains unclear and much debated, with contradictory results. Methods: We describe here the case of a 37-year-old man with ventilator-associated bacteraemic CRAB pneumonia in an intensive care unit. He was initially treated with a combination of colistin and tigecycline, and was then switched onto colistin and cefiderocol. We then used a new accessible protocol to test 30 CRAB isolates (OXA-23/OXA-24/OXA-58/NDM-1) for adaptive resistance to cefiderocol (ARC) after exposure to this drug. Results: After clinical failure with the initial combination, we noted a significant clinical improvement in the patient on the second combination, leading to clinical cure. No ARC was detected in the two OXA-23 case-CRAB isolates. All NDM-1 CRAB isolates were resistant to cefiderocol in standard tests; the OXA-23, OXA-24 and OXA-58 CRAB isolates presented 84.2 %, 50 % and 0 % ARC, respectively. Conclusions: ARC is not routinely assessed for CRAB isolates despite frequently being reported in susceptible isolates (69.2 %). Subpopulations displaying ARC may account for treatment failure, but this hypothesis should be treated with caution in the absence of robust clinical data. The two main findings of this work are that (i) cefiderocol monotherapy should probably not be recommended for OXA-23/24 CRAB infections and (ii) the characterisation of carbapenemases in CRAB strains may be informative for clinical decision-making.

Impact of automatic tools for detecting new lesions on therapeutic strategies offered to patients with MS by neurologists.

BACKGROUND: Automatic tools for detecting new lesions in patients with MS between two MRI scans are now available to clinicians. They have been assessed from the radiologist's point of view, but their impact on the therapeutic strategies that neurologists offer their patients has not yet been documented. OBJECTIVES: To compare neurologist's decisions according to whether a lesion detection support system had been used and describe variability between neurologists on decision-making for the same clinical cases. METHODS: We submitted 28 clinical cases associated with pairs of MRI images and radiological reports (produced by the same radiologist without vs. with the help of a system to detect new lesions) to 10 neurologists who regularly follow patients with MS. They examined each clinical case twice (without vs. with support system) in two sessions several weeks apart, and their patient management decisions were recorded. RESULTS: There was considerable variability between neurologists on decision-making (both with and without support system). When the support system had been used, neurologists more often made changes to patient management (75 % vs. 68 % of cases, p = 0.01) and spent significantly less time analyzing the clinical cases (249 s vs. 216 s, p == 3.10-4). CONCLUSION: The use of a lesion detection support system has an impact not only on radiologists' reports, but also on neurologists' subsequent decision-making. This observation constitutes another strong argument for promoting the wider use of such systems in clinical routine. However, despite their use, there is still considerable variability in decision-making across neurologists, which should encourage us to refine the guidelines.

The « patient casting ¼: a key decision in orthognathic surgery / Le « casting du patient ¼: clé de décision en chirurgie orthognathique

Introduction: The surgical orthodontic patient is a patient whose management is specific. The success of this protocol goes beyond of the right indication and the control of the pre-surgical orthodontic preparation of the treatment. The coordination revolves around a multidisciplinary team, namely an orthodontist, a maxillofacial surgeon, a physiotherapist, a speech therapist, a general practitioner, etc. but also with the collaboration of a specialized psychotherapist. Material and Method: Does the ideal « patient ¼ exist in orthognathic surgery? The decision criteria are morphological (occlusal, aesthetic and cephalometric) but also psychosocial. Results: A new classification called « psychological ¼ is proposed in this article. Conclusion: This new classification can be considered as a key decision in the « casting ¼ of the surgical orthodontic patient and represents a first basis for further investigations in this field.

Introduction: Le patient orthodontique chirurgical est un patient dont la prise en charge est spécifique. La réussite de ce protocole va au-delà de la pose de la bonne indication et de la maîtrise de la préparation orthodontique pré-chirurgicale du traitement. La coordination s'articule autour d'une équipe pluridisciplinaire, à savoir un orthodontiste, un chirurgien maxillofacial, un kinésithérapeute, un orthophoniste, un omnipraticien, entre autres, mais également avec la collaboration d'un psychothérapeute spécialisé. Matériel et méthode: Le « patient idéal ¼ existe-t-il en chirurgie orthognathique ? Les critères de décisions sont morphologiques (occlusaux, esthétiques et céphalométriques), mais aussi psycho-sociaux. Résultats: Une nouvelle classification dite « psychologique ¼ est proposée dans cet article. Conclusion: Cette nouvelle classification peut être considérée comme une clé de décision dans le « casting ¼ du patient orthodontique chirurgical et représente une première base pour de plus amples investigations dans ce domaine.

68Ga-PSMA PET-CT and PSMA score affecting therapeutic decision-making in high-risk prostatic carcinoma.

Purpose: This research study was conducted to evaluate the impact of (68Ga)-tagged prostatic-specific membrane antigen (68Ga-PSMA) positron emission tomography and computed tomography (PET-CT), compare its role with conventional radiology in early staging of high-risk prostate cancer, and calculate the PSMA score evaluating its usefulness in 68Ga-PSMA PET-CT reporting in our patient population. Material and methods: 68Ga-PSMA PET-CT of 65 high-risk cases of prostate cancer was performed for staging purpo-ses. Any change in disease stage was noted after 68Ga-PSMA PET-CT findings and PSMA score leading to a change in the management plan. Results: Change in disease stage post-PSMA imaging was seen in 39% cases, high PSMA score (03) was noted in > 80% of upstaged cases, while low score (0) and (1) was seen in 65% and 35% down-staged individuals, respectively. Change in therapeutic decision-making was observed in 32% (21) of patients. Conclusions: 68Ga-PSMA PET-CT scans have a significant influence on the planned clinical management of high-risk prostate cancer patients; hence, they can be utilized as a replacement for radiological imaging tools, particularly in the detection of pelvic nodal and distant metastatic disease. PSMA score can be considered as an effective tool in standardized reporting of 68Ga-PSMA imaging.

Optimizing therapeutic decision-making for off-label medicines use: A scoping review and consensus recommendations for improving practice and research.

PURPOSE: Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research. METHODS: We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers. RESULTS: We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations. CONCLUSIONS: We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.

Factors affecting the therapeutic decision / Facteurs influençant la décision thérapeutique

Introduction: Like the majority of medical professions, odontology is a regulated profession whose exercise is subject to legal provisions. Material and Method: The bases of these regulatory obligations are detailed and analysed, in particular the obligations concerning the relationship with patients, their information and obtaining their consent prior to any treatment. The obligations of the practitioner himself are then specified. Conclusion: Compliance with regulatory provisions is intended to provide a secure framework for practice and to promote a good patient-practitioner relationship.

Introduction: Comme la majorité des professions médicales, l'odontologie est une profession réglementée dont l'exercice est soumis à des dispositions légales. Matériel et méthode: Les fondements de ces obligations réglementaires sont détaillés et analysés. En particulier, les obligations concernant la relation avec les patients, leur information et l'obtention préalable à tout traitement de leur consentement. Les obligations incombant au praticien lui-même sont précisées ensuite. Conclusion: Le respect des dispositions réglementaires a pour but de procurer un cadre d'exercice sécurisé et de favoriser une bonne relation patient-praticien.

A scoping review of therapeutic reasoning process research.

Therapeutic reasoning is when the purpose, task, or goal for engaging in reasoning is to determine the patient's management plan. As the field's understanding of the process of therapeutic reasoning is less well understood, we focused on studies that collected data on the process of therapeutic reasoning. To synthesize previous studies of therapeutic reasoning characteristics, methodological approaches, theoretical underpinnings, and results. We conducted a scoping review with systematic searching for English language articles with no date limits. Databases included MEDLINE, CINAHL Plus, Scopus, Embase, Proquest Dissertations and Theses Global, and ERIC. Search terms captured therapeutic reasoning in health professions education research. Initial search yielded 5450 articles. The title and abstract screening yielded 180 articles. After full-text review, 87 studies were included in this review. Articles were excluded if they were outside health professions education, did not collect data on the process of therapeutic reasoning, were not empirical studies, or not focused on therapeutic reasoning. We analyzed the included articles according to scoping questions using qualitative content analysis. 87 articles dated from 1987 to 2019 were included. Several study designs were employed including think-aloud protocol, interview and written documentation. More than half of the articles analyzed the data using qualitative coding. Authors often utilized several middle-range theories to explain therapeutic reasoning processes. The hypothetico-deductive model was most frequently mentioned. The included articles rarely built off the results from previous studies. Six key result categories were found: identifying themes, characterizing and testing previous local theory, exploring factors, developing new local theory, testing tools, and testing hypothesis. Despite the cast body of therapeutic reasoning research, individual study results remain isolated from previous studies. Our future recommendations include synthesizing pre-existing models, developing novel methodologies, and investigating other aspects of therapeutic reasoning.

Criteria Associated with Treatment Decisions in Juvenile Idiopathic Arthritis with a Focus on Ultrasonography: Results from the JIRECHO Cohort.

BACKGROUND: The treatment of children with juvenile idiopathic arthritis (JIA) to prevent disability is a major challenge in paediatric rheumatology. The presence of synovitis, which is difficult to detect in children, is associated with structural damage. Musculoskeletal ultrasonography (MSUS) can be used in patients with JIA to reveal subclinical synovitis. OBJECTIVE: The primary aim was to determine whether the use of MSUS was associated with therapeutic modification in patients with JIA. The secondary aim was to identify other factors associated with therapeutic decisions. METHODS: We conducted an observational study based on the JIRECHO multi-centre cohort, which was developed to provide a systematic MSUS follow-up for patients with JIA. Follow-up occurred every 6 months and included clinical and MSUS examinations. We included children who underwent MSUS of the elbows, wrists, second metacarpophalangeal joints, knees and ankles, which was performed by expert sonographers. Clinical and biological data, disease activity scores and information on therapeutics were collected. RESULTS: A total of 185 visits concerning 112 patients were recorded. Three groups were defined according to the therapeutic decision: escalation (22%, n = 40), de-escalation (14%, n = 26) or stable (64%, n = 119). In the "therapeutic escalation" group: the presence of ultrasonographic synovitis in B-mode and the presence of grade 2 or 3 synovitis in B-mode were not significantly more frequent than in the "stable therapeutic or de-escalation" group (80% versus 65%, p = 0.06; 33% versus 19%, p = 0.06), and the patient's and physician's visual analogue scale (VAS) scores, the clinical JADAS and the C-reactive protein level were significantly higher, but only physician's VAS score remained in the model of logistic regression. In the "therapeutic de-escalation" group: there was no difference in the presence of US synovitis compared with the "stable therapeutic or escalation" group (62% versus 69%, p = 0.48). CONCLUSION: Even though US synovitis tended to be more frequent in patients with therapeutic escalation, the study did not show that the presence of synovitis in MSUS was statistically associated with therapeutic modifications in patients with JIA. Treatment remained stable despite the presence of US synovitis.

Development and Pilot Testing of the OTC Coach Software to Support Student Pharmacist Learning.

Description of the problem: Pharmacy students are expected to learn how condition and patient-specific factors influence medication decision-making. Our objective was to create an interactive learning tool that would support students as they learn how individual factors change over-the-counter (OTC) medication recommendations. Description of the innovation: OTC Coach was created to allow student pharmacists to practice making recommendations about OTC medications. First year student pharmacists enrolled in a required self-care therapeutics course were given access to the optional OTC Coach, which included electronic decision algorithms for 10 topics. Student perceptions were collected via an online survey. Critical analysis: Two-thirds of the first-year students enrolled in the self-care therapeutics course activated their OTC Coach account (n=53/79, 67%). Among the students who completed the survey and reported using the tool (n=60/75, 80%), there was agreement that it help them learn the course material (78%), increased their confidence in making appropriate therapeutic recommendations (78%), increased their confidence when answering examination questions (63%), and improved their examination performance (61%). Next steps: Implementing an electronic tool positively supported student learning about OTC medication recommendations, according to student self-report. The tool is being expanded to include an option for students to generate a series of scenarios with randomized patient and condition factors to further allow students to efficiently practice making repeated patient-centered recommendations.

Exploring Music Therapists' Experiences With and Perceptions About Copyrighted Music: A Thematic Analysis.

Patient-preferred music is often copyrighted music; prior research, however, has paid scant attention to music therapists' understanding and use of copyrighted music. To fill a gap in the literature, this exploratory study sought to understand music therapists' experiences and perceptions about permissible therapeutic uses of copyrighted music. Semi-structured interviews were conducted with 18 board-certified music therapists working in the United States. Collectively, these participants had over 300 years of professional experience. The interview transcripts were analyzed using an inductive approach to thematic analysis. Five main themes were identified: (1) copyright concerns created a complex psychological burden; (2) therapeutic needs warranted use of copyrighted music; (3) perceptions varied on permissible therapeutic practices using copyrighted music; (4) varied sources informed an understanding of copyright law; and (5) copyright clarity was needed to reduce the psychological burden. These themes suggest that psychological stress was produced by copyright uncertainty coupled with attempts by participants to satisfy diverse interests and protect multiple stakeholders, including patients, employers, their profession, and the law. Our findings suggest that a lack of clarity about permissible uses of copyrighted music can complicate music therapists' decision-making about appropriate therapeutic interventions. Clarity on permissible therapeutic uses of music could yield benefits for music therapists, patients, and the community.

Extrahepatic Disease in Hepatocellular Carcinoma: Do We Always Need Whole-Body CT or Is Liver MRI Sufficient? A Subanalysis of the SORAMIC Trial.

Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC.

[Colorectal cancer and preoperative geriatric assessment]. / Cancer colorectal et évaluation gériatrique préopératoire.

With the ageing of the population and the increase in the incidence of cancer in the population over 75 years of age, a partnership between geriatricians and oncologists is becoming necessary to optimise the management of these patients. There is great variability in the profiles of elderly patients and age cannot be the only criterion of the decision making. Thus, it is necessary to identify patients who will benefit from an in-depth geriatric assessment (IGA) and the G8 screening tool used in oncology consultations allows to do so. The EGA offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status of the person, and has been shown to have prognostic value for survival and relevance in guiding treatment choices.

Chronicity and the patient's decision-making work. The case of an advanced cancer patient.

This paper focuses on the particular situation of an advanced cancer patient whose condition has taken a chronic turn. We argue that chronicity of this kind sometimes falls at the frontier of Evidence Based Medicine because the uncertainty about the patient's condition can lead physicians to resort to clinical trials or non-licensed drugs to prevent the disease from progressing. This situation leaves plenty of scope for individual adjustments between patients and their doctors. Advanced cancer is regarded here not just as a biological event but as a chronic illness and a 'negotiated reality'. We argue that the chronicity of advanced cancer patients' situation broadens the patients' scope for 'work', and we have called this specific type of patient's work 'decision-making work'. This paper is based on a case study focusing on Patrick, a middle-aged Frenchman with metastatic lung cancer who underwent oncological treatment for seven years and was strongly determined to find new therapeutic options even if this meant having to go abroad. He actively orchestrated his therapeutic itinerary by reorganising his relationships with the medical world and coordinating the physicians' work. His particular social position enabled Patrick to bypass some of the current medical rules and to reorganise the usual pattern of distribution of medical responsibilities. The chronicity of his condition placed him at the very frontier of the health care system.

[Oncogeriatric assessment: The first step in personalizing cancer treatment in the elderly]. / L'évaluation oncogériatrique : la première étape de la personnalisation du traitement du cancer du sujet âgé.

With aging worldwide population and the high incidence of cancer in the population of people over 75 years old, there is a need for oncologists and geriatricians to strengthen their collaboration to improve elderly patients care. Complexity of cancer and aging issues must be considered simultaneously to establish a personalized care plan. Thus, the G8 is a screening tool that allows to identify patients who should benefit from a geriatric assessment, which is a key step in the management process. This specific evaluation offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status and has demonstrated its prognostic value in terms of choice of treatment but also in terms of patient survival. In nearly 20% of cases, the geriatric assessment leads to a change in the choice of treatment, and at one year the initial care plan is not carried out in a quarter of cases. The presence of malnutrition and functional impairment leading to dependence on basic activities of daily living had a significant impact on this change in therapeutic choice. Survival is not only impacted by malnutrition and functional impairment but also by the presence of severe comorbidities and thymic and neurocognitive impairment. The patient's choice must remain at the center of the elaboration of the care plan with the oncologists and geriatricians in order to propose the most appropriate treatment for his or her situation.

Therapeutic Decision-Making and Outcomes in Elderly Patients With Severe Symptomatic Aortic Stenosis: Prognostic Implications of Elderly Patients' Initial Decisions.

Background: Despite clear indications for intervention, therapeutic decision-making for elderly patients with severe symptomatic aortic stenosis (AS) remains a complex issue due to the wide variation in individual risk profiles and the involvement of patients' subjective preferences. We aimed to investigate the reasons leading to the decisions against intervention and the consequences thereof on survival. Methods: Data were derived from the China Elderly Valve Disease (China-DVD) Cohort Study on patients aged ≥60-year-old with severe symptomatic AS consecutively enrolled between September to December 2016. Patients were analyzed according to the initial therapeutic decisions made by consensus between patients and physicians at the time of the index evaluation: intervention group (patients who were evaluated as suitable for intervention and accepted the treatment proposal); patient-refusal group (patients who were evaluated as suitable for intervention but refused due to subjective preferences); physician-deny group (patients who were denied intervention by physicians after evaluation). The least absolute shrinkage and selection operator (LASSO)-penalized logistic regression model was used to identify the factors associated with physicians' decisions against intervention. Twelve-month survival was analyzed using Cox proportional hazards models, with multivariate adjustment using inverse probability weighting (IPW). Results: Among the enrolled 456 elderly patients with severe symptomatic AS, 52 (11.4%) patients refused intervention and 49 (10.7%) patients were denied intervention by their physicians. LASSO-penalized logistic regression model identified that reduced left ventricular ejection fraction and increased EuroSCORE-II were strongly associated with physicians' decisions against intervention. At 12-month follow-up, only 8 (15.4%) patients who initially refused the intervention proposal underwent the subsequent intervention, with an average delay of 195 days. Patients' initial decisions against intervention were significantly associated with 12-month mortality, even after IPW adjustment (Hazard ratio: 2.61; 95% confidence interval: 1.09-6.20; P = 0.031). Conclusions: The decision against intervention was taken in about one-fifth of elderly patients with symptomatic severe AS, half of which were due to patients' subjective preferences. Surgical risk remains the primary concern for physicians when making therapeutic decisions. Elderly patients' initial decisions against intervention have a profound impact on subsequent intervention rates and prognosis, and therefore should be treated as a "risk factor" at the subjective level. Clinical Trial Registration: clinicaltrials.gov/ct2/show/NCT02865798, China elDerly Valve Disease (China-DVD) cohort study (NCT02865798).

Identification of patients with relapsing multiple sclerosis eligible for high-efficacy therapies.

Relapsing multiple sclerosis (RMS) presents a highly variable clinical evolution among patients, and its management should be personalized. Although there is no cure at present, effective disease-modifying therapies (DMTs) are available. Selection of the most appropriate DMT for each patient is influenced by several clinical, radiological and demographic aspects as well as personal preferences that, at times, are not covered in the regulatory criteria. This may be a source of difficulty, especially in certain situations where so-called 'high-efficacy DMTs' (usually considered second-line) could be of greater benefit to the patient. In this narrative review, we discuss evidence and experience, and propose a pragmatic guidance on decision-making with respect to the indication and management of high-efficacy DMT in adult patients with RMS based on expert opinion.

Integrating proteomics into precision oncology.

DNA sequencing and RNA sequencing are increasingly applied in precision oncology, where molecular tumor boards evaluate the actionability of genetic events in individual tumors to guide targeted treatment. To work toward an additional level of patient characterization, we assessed the abundance and activity of 27 proteins in 134 patients whose tumors had previously undergone whole-exome and RNA sequencing within the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) program of National Center for Tumor Diseases, Heidelberg. Proteomic and phosphoproteomic targets were selected to reflect the most relevant therapeutic baskets in MASTER. Among six different therapeutic baskets, the proteomic data supported treatment recommendations that were based on DNA and RNA analyses in 10% to 57% and frequently suggested alternative treatment options. In several cases, protein activities explained the patients' clinical course and provided potential explanations for treatment failure. Our study indicates that the integrative analysis of DNA, RNA and protein data may refine therapeutic stratification of individual patients and, thus, holds potential to increase the success rate of precision cancer therapy. Prospective validation studies are needed to advance the integration of proteomic analysis into precision oncology.

Therapeutic decision-making in primary care pharmacy practice.

BACKGROUND: Therapeutic decision-making is a core element of pharmacy practice, however, little has been documented about how it is enacted in practice and how it can be theorised. OBJECTIVE(S): This study aims to contribute to pharmacy education and practice theory by investigating the correspondence between explanations from primary care pharmacists in clinical practice roles about how they make decisions related to medicines therapy and a theoretical model of therapeutic decision-making. METHODS: In this qualitative study, interview data from 10 pharmacists in primary care settings were analysed using a general inductive approach. The emergent themes were compared to a theoretical model of therapeutic decision-making. RESULTS: Eight themes were identified from the explanations of how participants were making therapeutic decisions in practice. The themes were found to correspond to at least one of the four steps of therapeutic decision-making in the model. Themes corresponding to the information gathering step were described most vividly, whereas, the themes corresponding to the reasoning, judgement, and decision steps were less well-articulated. CONCLUSIONS: These findings suggest that the theoretical model can be useful to interpret empirical data about therapeutic decision-making in practice. These findings might provide a means for pharmacists to adopt language to better describe the steps in their therapeutic decision-making process to others, and especially, their colleagues and patients. Findings can be used by pharmacy educators to design learning opportunities for students about therapeutic decision-making.

Non-invasive cardiac allograft rejection surveillance: reliability and clinical value for prevention of heart failure.

Allograft rejection-related acute and chronic heart failure (HF) is a major cause of death in heart transplant recipients. Given the deleterious impact of late recognized acute rejection (AR) or non-recognized asymptomatic antibody-mediated rejection on short- and long-term allograft function improvement of AR surveillance and optimization of action strategies for confirmed AR can prevent AR-related allograft failure and delay the development of cardiac allograft vasculopathy, which is the major cause for HF after the first posttransplant year. Routine non-invasive monitoring of cardiac function can improve both detection and functional severity grading of AR. It can also be helpful in guiding the anti-AR therapy and timing of routine surveillance endomyocardial biopsies (EMBs). The combined use of EMBs with non-invasive technologies and methods, which allow detection of subclinical alterations in myocardial function (e.g., tissue Doppler imaging and speckle-tracking echocardiography), reveal alloimmune activation (e.g., screening of complement-activating donor-specific antibodies and circulating donor-derived cell-free DNA) and help in predicting the imminent risk of immune-mediated injury (e.g., gene expression profiling, screening of non-HLA antibodies, and circulating donor-derived cell-free DNA), can ensure the best possible surveillance and management of AR. This article gives an overview of the current knowledge about the reliability and clinical value of non-invasive cardiac allograft AR surveillance. Particular attention is focused on the potential usefulness of non-invasive tools and techniques for detection and functional grading of early and late ARs in asymptomatic patients. Overall, the review aimed to provide a theoretical and practical basis for those engaged in this particularly demanding up-to-date topic.