Questions In Clinical Practice Research Articles

(CDK) 4/6 inhibitors: An effective treatment for homologous recombination deficient (HRD) luminal breast cancers (BC)?

e13100 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) still represents the best 1st-line choice for hormone receptor (HR) positive(+)/HER2 negative(-) metastatic breast cancer (MBC) patients (pts). Approximately 8% of pts with HR+ BC harbors germline BRCA mutation (g BRCAmt). The interaction between Cyclin/CDK pathway, endocrine receptor (ER) and Breast Cancer gene 1/2 (BRCA1/2) is complex and evidence reported so far, await confirmation in the context of future randomized clinical trials. So far, limited data exist about treatment effectiveness of CDK4/6i in homologous recombination deficiency (HRD) Luminal BC. A current frequent question in clinical practice is which additional adjuvant therapy to prioritize for luminal BRCA tumors (tu), considering the approval of both CDK4/6i andpoly ADP ribose polymerase (PARP) inhibitors in this scenario. Considering potential impacts of genetic instability in tu biology, such as potential loss of Rb protein related to Loss of Heterozygosity (LOH) of BRCA2 as a primary resistance mechanism in CDK4/6i, we sought to analyze the clinical results of that drug in tu with genetic instability. Methods: We retrospectively analyzed real-world outcomes of CDK4/6i performance in HR+/HER2- MBC treated in a single institution, with focus in clinical outcomes of HRD BC. germline HR genes status and somatic phosphatidylinositol 3-kinase (PIK3CA) status were also analyzed. Results: A total of 384 consecutive MBC pts treated with CDK4/6i were included in this study. The most used CDK4/6i was palbociclib (40,6%), followed by ribociclib (29,8%) and abemaciclib (29,2%). Considering the whole cohort PFSm 30months (95%IC 26-34) and OSm were 56 months (95%IC 52-60) No differences in PFS or OS was observed among the 3 CDK4/6i. Median age of the cohort was 60 years old. 38.5% were premenopause Pts and 59.9% were postmenopause. A total of 149 (39%) pts performed germline screening. Between 19 pts with gHR mt, 12 were BRCA1/2 mt (just one BRCA1). The other were: 2 PALB2, 2 CHEK2, 1 ATM, 1 RAD51D, 1 RAD51C mt. So far, no differences in PFS ou OS was observed in the presence of BRCA 1/2 or other gHR mt. Nevertheless, PIK3CA mt was tested in 142 pts, 51 were positives. That mt was a predictor of worse OS (55m; 95%IC 45-65) x 63m (95%IC 56-69), p 0,019. Conclusions: The results of this real-world study suggest that treatment outcomes with CDK4/6i may be worse in pts with HRD tu due to potential differences in tu biology. Future exploration in larger samples of patients who have had biomarker testing is ongoing. Patients with Pik3CA mt treated with CDK4/6i presented worse clinical outcomes.

Making causal inferences from transactional data: A narrative review of opportunities and challenges when implementing the target trial framework.

The target trial framework has emerged as a powerful tool for addressing causal questions in clinical practice and in public health. In the healthcare sector, where decision-making is increasingly data-driven, transactional databases, such as electronic health records (EHR) and insurance claims, present an untapped potential for answering complex causal questions. This narrative review explores the potential of the integration of the target trial framework with real-world data to enhance healthcare decision-making processes. We outline essential elements of the target trial framework, and identify pertinent challenges in data quality, privacy concerns, and methodological limitations, proposing solutions to overcome these obstacles and optimize the framework's application.

A potential impact of the immunological profile of current covid-19 vaccines on pregnancy outcomes

The potential impact of COVID-19 vaccination on pregnancy is still a topic of question in clinical practice. This short communication briefly presents the impact of immunological aspects of current covid-19 vaccines on pregnancy outcomes.

Pragmatic trial design to compare real-world effectiveness of different treatments for inflammatory bowel diseases: the PRACTICE-IBD European consensus.

Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The European consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid comparative pragmatic studies in inflammatory bowel diseases (IBDs). Statements were issued by a panel of 11 European experts in IBD management and trial methodology on four main topics: (I) study design; (II) eligibility, recruitment and organization, flexibility; (III) outcomes; (IV) analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement (1 to 9; cut-off ≥7 for approval) with the statements by 18 additional European experts in IBD. At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: 7 for study design, 6 for eligibility, recruitment and organization, flexibility, 8 for outcomes, and 4 for analysis. Pragmatic randomized clinical trials can address important questions in IBD clinical practice, and may provide complementary high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality pragmatic clinical trials that can aid decision making in choosing a management strategy for IBDs.

Two Cases of Emergency Tracheostomy After Head and Neck Photoimmunotherapy.

Head and neck photoimmuno-therapy (HN-PIT) has been an insured treatment in Japan for approximately three years. The number of treatments has gradually increased to over 350 cases. However, there are still various questions in actual clinical practice, including laryngeal edema. Therefore, it is vital to carefully explain in advance to patients the possibility of laryngeal edema occurring and obtaining consent for tracheostomy as a prophylactic or emergency measure. At our institution, 44 HN-PIT cycles were performed in 23 patients between January 2021 and October 2023. Of these, we experienced two cases in which preventive tracheostomy was not performed because the risk of laryngeal edema was considered low; however, laryngeal edema developed after treatment, and an emergency tracheostomy had to be performed. Case 1 was a patient in his 70s with a local recurrence of mandibular gingival carcinoma. HN-PIT using cylindrical diffusers was performed on the target lesion, extending from the lateral wall of the oropharynx to the soft palate. Case 2 was also a patient in his 70s with carcinoma of the mid-pharynx. HN-PIT was performed using a frontal diffuser to target lesions extending from the soft palate to the buccal mucosa. Notably, both patients developed laryngeal edema after HN-PIT, and an emergency tracheostomy had to be performed. HN-PIT treatment is still being established through a trial-and-error method and is still incomplete.

European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours.

This ENETS guidance paper for well-differentiated nonfunctioning pancreatic neuroendocrine tumours (NF-Pan-NET) has been developed by a multidisciplinary working group, and provides up-to-date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF-Pan-NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF-Pan-NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

The Future Ain't What It Used to Be…Out With the Old…In With the Better: Antibacterial Resistance Leadership Group Innovations.

Clinical research networks conduct important studies that would not otherwise be performed by other entities. In the case of the Antibacterial Resistance Leadership Group (ARLG), such studies include diagnostic studies using master protocols, controlled phage intervention trials, and studies that evaluate treatment strategies or dynamic interventions, such as sequences of empiric and definitive therapies. However, the value of a clinical research network lies not only in the results from these important studies but in the creation of new approaches derived from collaborative thinking, carefully examining and defining the most important research questions for clinical practice, recognizing and addressing common but suboptimal approaches, and anticipating that the standard approaches of today may be insufficient for tomorrow. This results in the development and implementation of new methodologies and tools for the design, conduct, analyses, and reporting of research studies. These new methodologies directly impact the studies conducted within the network and have a broad and long-lasting impact on the field, enhancing the scientific value and efficiency of generations of research studies. This article describes innovations from the ARLG in diagnostic studies, observational studies, and clinical trials evaluating interventions for the prevention and treatment of antibiotic-resistant bacterial infections.

Performance evaluation of ChatGPT, GPT-4, and Bard on the official board examination of the Japan Radiology Society.

Herein, we assessed the accuracy of large language models (LLMs) in generating responses to questions in clinical radiology practice. We compared the performance of ChatGPT, GPT-4, and Google Bard using questions from the Japan Radiology Board Examination (JRBE). In total, 103 questions from the JRBE 2022 were used with permission from the Japan Radiological Society. These questions were categorized by pattern, required level of thinking, and topic. McNemar's test was used to compare the proportion of correct responses between the LLMs. Fisher's exact test was used to assess the performance of GPT-4 for each topic category. ChatGPT, GPT-4, and Google Bard correctly answered 40.8% (42 of 103), 65.0% (67 of 103), and 38.8% (40 of 103) of the questions, respectively. GPT-4 significantly outperformed ChatGPT by 24.2% (p < 0.001) and Google Bard by 26.2% (p < 0.001). In the categorical analysis by level of thinking, GPT-4 correctly answered 79.7% of the lower-order questions, which was significantly higher than ChatGPT or Google Bard (p < 0.001). The categorical analysis by question pattern revealed GPT-4's superiority over ChatGPT (67.4% vs. 46.5%, p = 0.004) and Google Bard (39.5%, p < 0.001) in the single-answer questions. The categorical analysis by topic revealed that GPT-4 outperformed ChatGPT (40%, p = 0.013) and Google Bard (26.7%, p = 0.004). No significant differences were observed between the LLMs in the categories not mentioned above. The performance of GPT-4 was significantly better in nuclear medicine (93.3%) than in diagnostic radiology (55.8%; p < 0.001). GPT-4 also performed better on lower-order questions than on higher-order questions (79.7% vs. 45.5%, p < 0.001). ChatGPTplus based on GPT-4 scored 65% when answering Japanese questions from the JRBE, outperforming ChatGPT and Google Bard. This highlights the potential of using LLMs to address advanced clinical questions in the field of radiology in Japan.

P79 A multidisciplinary expert consensus on the assessment of and support for mental health in children and young people living with skin conditions

Abstract Psychological and mental health concerns are common in children and young people (CYP) living with skin conditions and can have a profound impact on wellbeing. However, there is limited guidance on how best to assess and support the mental health of this population, who are at risk of poor health outcomes. The British Society for Paediatric and Adolescent Dermatology (BSPAD) formed a working group to address the mental health needs of CYP with skin conditions, including hair and nails. A systematic review, appraisal of literature and a national survey were carried out, and a multidisciplinary consensus guideline group was convened, comprising dermatologists with expertise in paediatric dermatology and psychodermatology, psychologists, psychiatrists, general practitioners, paediatricians and specialist nurses. Two multidisciplinary virtual panel meetings took place: (i) an initial meeting to discuss the scope, review the current evidence and identify areas for development and (ii) a second meeting to agree the content and wording of the recommendations. The primary objective was to provide consensus-based guidance on the assessment and monitoring of, and support for, mental health in CYP with skin conditions. Secondary objectives were to address important practical clinical questions relating to primary guidance objectives and provide audit and research recommendations. The expert panel achieved consensus on 11 recommendations for health workers managing CYP with skin conditions. A new patient-completed history-taking aid called ‘You and Your Skin’ was developed and is being piloted. The recommendations focus on improved mental health assessments for CYP presenting with a skin condition, with clinical guidance and suggested screening measures included. Information is given regarding accessing psychological support for CYP when required, and recommendations were provided for training in mental health and neurodiversity for staff. The methodology and recommendations will be presented in full. Embedding a psychosocial approach within services treating CYP with skin disease should ensure that CYP with psychological needs are able to be identified, listened to, supported and treated. This is likely to improve health outcomes.

PA09 (P79) A multidisciplinary expert consensus on the assessment of and support for mental health in children and young people living with skin conditions

Abstract Psychological and mental health concerns are common in children and young people (CYP) living with skin conditions, and can have a profound impact on wellbeing. However, there is limited guidance on how best to assess and support the mental health of this population, who are at risk of poor health outcomes. The British Society for Paediatric and Adolescent Dermatology formed a working group to address the mental health needs of CYP with skin conditions, including hair and nails. A systematic review, appraisal of literature and a national survey were carried out, and a multidisciplinary consensus guideline group was convened, comprising dermatologists with expertise in paediatric dermatology and psychodermatology, psychologists, psychiatrists, general practitioners, paediatricians and specialist nurses. Two multidisciplinary virtual panel meetings took place: (i) an initial meeting to discuss the scope, review the current evidence and identify areas for development; and (ii) a second meeting to agree the content and wording of the recommendations. The primary objective was to provide consensus-based guidance on the assessment and monitoring of, and support for, mental health in CYP with skin conditions. Secondary objectives were to address important practical clinical questions relating to primary guidance objectives, and provide audit and research recommendations. The expert panel achieved consensus on 11 recommendations for health workers managing CYP with skin conditions. A new patient-completed history-taking aid called ‘You and Your Skin’ was developed and is being piloted. The recommendations focus on improved mental health assessments for CYP presenting with a skin condition, with clinical guidance and suggested screening measures included. Information regarding accessing psychological support for CYP when required is given, and recommendations were provided for training in mental health and neurodiversity for staff. The methodology and recommendations will be presented in full. Embedding a psychosocial approach within services treating CYP with skin disease should ensure that CYP with psychological needs are able to be identified, listened to, supported and treated. This is likely to improve health outcomes.

Clinical Ethics Committee in an Oncological Research Hospital: two-years Report.

Clinical Ethics Committees (CECs) aim to support healthcare professionals (HPs) and healthcare organizations to deal with the ethical issues of clinical practice. In 2020, a CEC was established in an Oncology Research Hospital in the North of Italy. This paper describes the development process and the activities performed 20months from the CEC's implementation, to increase knowledge about CEC's implementation strategy. We collected quantitative data related to number and characteristics of CEC activities carried out from October 2020 to June 2022 using the CEC internal database. Data were reported descriptively and compared with data from the literature to provide a complete overview of the CEC's development and implementation process. The study has been conducted at the local health authority (LHA) of Reggio Emilia. It is a report of the activities provided by the CEC, where no HPs or patients were involved. The report is part of a larger study named EVAluating a Clinical Ethics Committee implementation process (EvaCEC), which has been approved by the Local Ethics Committee (AUSLRE Protocollo n° 2022/0026554 of 24/02/2022). EvaCEC is also the first author's PhD project. In total, the CEC performed 7 ethics consultations (EC), published three policies related to particular ethical questions of clinical and organizational practice, provided one educational online course on ethics consultation targeting employed HPs, and promoted a specific dissemination process among the different departments of the LHA. According to our results, the CEC widely fulfilled the standard threefold set of clinical ethics support services tasks (namely, ethics consultation, ethics education, and policy development), but further investigations are needed to evaluate the CEC's impact on clinical practice. Our findings may increase knowledge regarding the composition, role, and tasks of a CEC in an Italian setting, informing future strategies and efforts to regulate these institutions officially.

British Society for Paediatric and Adolescent Dermatology (BSPAD) assessment and support of mental health in children and young people (CYP) with skin conditions: A multi-disciplinary expert consensus statement and recommendations.

Psychological and mental health difficulties are common in children and young people (CYP) living with skin conditions and can have a profound impact on wellbeing. There is limited guidance on how best to assess and support the mental health of this population who are at risk of poor health outcomes. The primary objective was to provide consensus-based recommendations on the assessment and monitoring of and support for mental health difficulties in children and young people (CYP) with skin conditions (affecting the skin, hair and nails). The secondary objectives were to address practical clinical implementation questions relating to consensus guidance; and to provide audit and research recommendations. This set of recommendations has been developed with reference to the AGREE II instrument. A systematic review and literature appraisal was carried out. A multidisciplinary consensus group was convened with two virtual panel meetings taking place: an initial meeting to discuss the scope, review the current evidence and identify areas for development; the second to agree content and wording of the recommendations. Recommendations were then circulated to stakeholders, following which amendments were made and agreed by email. The expert panel achieved consensus on eleven recommendations for health workers managing CYP with skin conditions. A new patient completed history taking aid - 'You and Your Skin' was developed and is being piloted. The recommendations focus on improved mental health assessments for CYP presenting with a skin condition with clinical guidance and suggested screening measures included. Information is given regarding accessing psychological support for CYP when required and recommendations provided for training in mental health and neurodiversity for staff. Embedding a psychosocial approach within services treating CYP with skin disease should ensure that CYP with psychological needs are able to be identified, listened to, supported and treated. This is likely to improve health outcomes.

Selectief mutisme en autisme: een verkenning en aanbevelingen voor de praktijk

In recent years, the clinical view on selective mutism has shifted from willful silence in specific situations and with specific persons, to being anxious to communicate in social situations. These social communication difficulties make it challenging for clinicians to distinguish selective mutism from autism. Historically, selective mutism and autism could not be formally classifi ed side by side. Currently, however, there is a debate about whether these classifications can co-occur. This raises questions for clinical practice, such as what this means for the diagnostic and treatment process. In this review we will discuss these issues based on recent literature, and we will provide clinicians with recommendations for clinical practice.

Academic activity aims to early expose medical students to best prescribing practices

Prescribing medications is a significant clinical responsibility for medical providers. However, fresh medical graduates often report a lack of confidence in prescribing medications and answering drug-related questions in clinical practice. We implemented a course at Sulaiman AlRajhi University medical school to enhance medical training for student physicians to engage in optimal practices in prescribing medications. We designed an elective pharmacology course to optimize student physicians’ skills in prescription practices while also introducing them to the pharmacy and the duties of pharmacists as healthcare providers. The course targeted second-year students as we desired early exposure. Furthermore, we identified objectives that were deemed essential to acquire during the course and assessment methods. We analyzed the data of 56 student physicians who participated in the elective pharmacology course during the academic years 2019–2020 and 2020–2021. Collectively, there was a negative shift in the performance of student physicians in the academic year 2020-2021 compared to the previous year 2019-2020, with 5.2% fewer students getting grades of A+ and 17.8% more students getting D grades or lower. The grades significantly differed between both years X2(8, N=56) = 27.61, p = .000). Our data reported high satisfaction and confidence in the prescription skills of the student physicians who underwent the course. However, to evaluate its full potential and assess its usefulness, we believe additional research and implementation of more prescribing skills exercises across all academic years is essential‎.

Fred J Boyd Oration 2021

Fred J Boyd Oration 2021

British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma in situ (Bowen disease) 2022.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of squamous cell carcinoma in situ (SCC in situ). The document aims to: offer an appraisal of all relevant literature up to 13th August 2021, focusing on any key developments; address important, practical clinical questions relating to the primary guideline objective; provide guideline recommendations and if appropriate research recommendations.

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials.

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.

Extracorporeal carbon dioxide removal for acute respiratory failure: a review of potential indications, clinical practice and open research questions.

Extracorporeal carbon dioxide removal (ECCO2R) is a form of extracorporeal life support (ECLS) largely aimed at removing carbon dioxide in patients with acute hypoxemic or acute hypercapnic respiratory failure, so as to minimize respiratory acidosis, allowing more lung protective ventilatory settings which should decrease ventilator-induced lung injury. ECCO2R is increasingly being used despite the lack of high-quality evidence, while complications associated with the technique remain an issue of concern. This review explains the physiological basis underlying the use of ECCO2R, reviews the evidence regarding indications and contraindications, patient management and complications, and addresses organizational and ethical considerations. The indications and the risk-to-benefit ratio of this technique should now be carefully evaluated using structured national or international registries and large randomized trials.

Clinical studies in amyotrophic lateral sclerosis.

The purpose of this review is to discuss the most important recent clinical studies in amyotrophic lateral sclerosis (ALS), including their impact on clinical practice, their methodology, and open questions to be addressed in the future. This article focuses on studies, which provided either a positive primary endpoint or positive post hoc analysis, including edaravone, sodium phenylbutyrate-taurursodiol, rasagiline, tofersen, and high-caloric, fat-rich nutrition. It also covers recent developments in the design of clinical ALS studies with regard to inclusion criteria, stratification factors, and outcome parameters. Recent clinical studies have indicated various substances to be considered for treatment of ALS. Edaravone has been approved by the US Food and Drug Association (FDA) but not by the European Medicines Agency (EMA), and further studies testing oral formulations are currently conducted. A follow-up study with sodium phenylbutyrate-taurursodiol is ongoing, while follow-up studies for rasagiline and high-caloric, fat-rich nutrition are planned. A phase III study with tofersen was negative but nevertheless yielded promising results. Important developments regarding the design of clinical ALS studies include the implementation of neurofilament light chain (NfL) levels as a standard outcome parameter and the consideration of progression rate for therapeutic response and stratification.

Issues of etiotropic therapy in conditions of ‘omicron’ strain of SARS-CoV‑2 spreading: Real practice

The article presents clinical examples of treatment of patients with COVID-19 diagnosed during the period of active spread of the ‘omicron’ strain. The results of symptomatic therapy and the need for the appointment of etiotropic drugs, including in the late stages of the disease, are considered, which raises the greatest number of questions in clinical practice. In the presented examples, patients received medicines approved by the current temporary guidelines for the diagnosis, treatment and prevention of COVID-19 of the Ministry of Health of the Russian Federation. The analysis of the course of the disease confirms the continuing need for the appointment of etiotropic therapy in the conditions of the spread of the ‘omicron’ variant, including in the second week of the disease. Umifenovir therapy as part of a comprehensive treatment regimen suspends the progression of COVID-19 and leads to relief of symptoms. Symptomatic treatment in the conditions of the spread of a new variant of the coronavirus omicron cannot replace etiotropic and pathogenetic therapy.