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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.
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.
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.
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.

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.

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.

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.

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.

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.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

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.