Delirium in geriatric patients

SummaryDelirium is the most common acute disorder of cognitive function in older patients. Delirium is life threatening, often under-recognized, serious, and costly. The causes are multifactorial, with old age and neurocognitive disorders as the main risk factors. Etiologies are various and multifactorial, and often related to acute medical illness, adverse drug reactions, or medical complications. To date, diagnosis is clinically based, depending on the presence or absence of certain features. In view of the multifactorial etiology, multicomponent approaches seem most promising for facing patients’ needs. Pharmacological intervention, neither for prevention nor for treatment, has been proven effective unanimously. This article reviews the current clinical practice for delirium in geriatric patients, including etiology, pathophysiology, diagnosis, prognosis, treatment, prevention, and outcomes.

A Bayesian Framework to Assess the Usability of Dry Powder Inhalers in a Cohort of Asthma Adolescents in Italy

The useability of DPIs (dry powder inhalers) depends on several factors that are influenced by the patients’ subjectivity and objectivity. The short-form global usability score (S-GUS), a specific tool for the quick ranking and comparison in real life of an inhaler’s usability, was used to investigate six of the most prescribed DPIs (Breezhaler, Diskus, Ellipta, Nexthaler, Spiromax, and Turbohaler) in consecutive asthma patients aged <18 years. A Bayesian indirect comparison (IC) was carried out to merge all pairwise comparisons between the six DPIs. Thirty-three subjects participated: eighteen tested Breezhaler, Spiromax, Nexthaler, and Ellipta simultaneously, while fifteen tested Breezhaler, Spiromax, Diskus, and Turbohaler. The estimates of the S-GUS, by the IC model, allowed us to rank the DPIs by their degree of usability: Ellipta, Diskus, and Spiromax were classified as “good to pretty good” (S-GUS > 15), while Spiromax, Turbohaler, and Breezhaler were classified as “insufficient” (S-GUS < 15). The multidomain assessment is recommended in asthma adolescents in order to approximate the effective usability of different DPIs as best as possible. The S-GUS proves particularly suitable in current clinical practice because of the short time required for its use in adolescents.

Evaluating a communication aid for return of genetic results in families with hypertrophic cardiomyopathy: A randomized controlled trial

Introduction: Genetic testing for hypertrophic cardiomyopathy (HCM) is considered a key aspect of management. Communication of genetic test results to the proband and their family members, can be a barrier to effective uptake. We hypothesized that a communication aid would facilitate effective communication, and sought to evaluate knowledge and communication of HCM risk to at-risk relatives. Methods: This was a prospective randomized controlled trial. Consecutive HCM patients attending a specialized clinic, who agreed to participate, were randomized to the intervention or current clinical practice. The intervention consisted of a genetic counselor-led appointment, separate to their clinical cardiology review, and guided by a communication booklet which could be written in and taken home. Current clinical practice was defined as the return of the genetic result by a genetic counselor and cardiologist, often as part of a clinical cardiology review. The primary outcome was the ability and confidence of the individual to communicate genetic results to at-risk relatives. Results: The a priori outcome of improved communication amongst HCM families did not show statistically significant differences between the control and intervention group, though the majority of probands in the intervention group achieved fair communication (n=13/22) and had higher genetic knowledge scores than those in the control group (7 +/- 3 versus 6 +/- 3). A total of 29% of at-risk relatives were not informed of a genetic result in their family. Conclusion: Communication amongst HCM families remains challenging, with nearly a third of at-risk relatives not informed of a genetic result. We show a significant gap in the current approach to supporting family communication about genetics.

Ethical challenges in palliative sedation of adults: protocol for a systematic review of current clinical practice guidelines

Introduction: This study aims to identify the full spectrum of ethical challenges of all forms of palliative sedation for adults as presented in current clinical practice guidelines (CPGs), and to determine whether CPGs specify ethical challenges of this therapy for cancer and non-cancer patients and, if so, how exactly they do this. To the best of our knowledge, no studies have yet investigated this topic. The purpose is purely descriptive; our aim is not to make any kind of normative judgements on these challenges. Nor is our aim to assess the quality of the CPGs. Methods and analysis : We will perform a systematic review of CPGs on palliative sedation for adults via five electronic databases, grey literature search tools, citation tracking, and contact with palliative care experts. Current CPGs validated by an international, national, or regional authority, published in English, German, French, Italian, or Polish, from 2000 to the date of the search, will be subjected to content analysis at the textual, linguistic, and thematic levels. This study protocol is reported in accordance with the PRISMA-P criteria and registered on PROSPERO. Discussion The results of our systematic review can help raise awareness and understanding of the complexity of ethical problems, rigorously guide reflection in this field, and be useful in elaborating ethical guidelines in an interdisciplinary approach, in order to have a positive impact on the quality of patient care, education and training, and research in respect of this complex and challenging practice.

OP437 Use Of Real-World Evidence In Survival Analysis Adjusting For Treatment Crossover In Cutaneous T-Cell Lymphoma

Real-World Evidence is useful for validating crossover adjustment approaches, particularly when the adjustment is required because a trial does not accurately reflect a health technology assessment (HTA)-relevant population. We use the MAVORIC trial advanced stage mycosis fungoides and Sézary syndrome cutaneous T-cell lymphoma population and data from the Hospital Episodes Statistics to explore and validate crossover adjustment methods.IntroductionThe MAVORIC trial compared mogamulizumab to vorinostat in patients with mycosis fungoides (MF) or Sézary syndrome (SS), subtypes of cutaneous T-cell lymphoma. However, the treatment comparison within MAVORIC may not represent an HTA relevant population from a UK perspective: (i) 72.6 percent of patients randomized to vorinostat switched to mogamulizumab and (ii) vorinostat is not used in current clinical practice in the UK. This study explores methods to adjust treatment effect estimates using different crossover adjustment methods and Real-World Evidence.This medicine is subject to additional monitoring. This will allow quick identification of new safety information. See www.mhra.gov.uk/yellowcard for how to report side effects.MethodsAn advanced stage (stage ≥IIB MF and all SS) population was included. Three methods were considered for treatment crossover adjustment. A synthetic control arm was created using the Hospital Episodes Statistics (HES) dataset. Predicted survival for the MAVORIC control arm, post-crossover adjustment, was compared to the HES to inform the selection of the appropriate methods for adjustment. A direct comparison between mogamulizumab (reweighted to represent the distribution of MF/SS patients in the HES) and the synthetic control was also conducted.ResultsFollowing crossover adjustment of the vorinostat arm, using the inverse probability of censoring weighting method, the overall survival (OS) hazard ratio (HR) estimate for mogamulizumab vs. vorinostat was 0.45 (95% confidence interval (CI): 0.19, 1.07). This adjustment method was considered the most appropriate based on an assessment of assumptions and a comparison of OS between the adjusted vorinostat data and the HES data. The OS HR estimate for reweighted mogamulizumab vs. synthetic control from HES was 0.33 (CI: 0.21, 0.50).ConclusionsReal World Evidence from the HES database can be used to validate crossover adjustment methods and to better reflect current clinical practice in the UK. Results using both methods support each other.

Current Clinical Practice for Thromboprophylaxis Management in Patients With Cushing’s Syndrome Across Reference Centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN)

Background: Cushing’s syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. Results: The majority of the RCs provided thromboprophylaxis to patients with CS (n=23/25), although only one center had a standardized thromboprophylaxis protocol (n=1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n=11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n=15/23). Factors influencing the initiation of thromboprophylaxis were ‘medical history of VTE’ (n=15/23) and ‘severity of hypercortisolism’ (n=15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n=23/23). Postoperatively, the majority of RCs reported ‘severe immobilization’ as an indication to start thromboprophylaxis in patients with CS (n=15/25). Most RCs (n=19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n=23/25). About half of these RCs (n=12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n=15/23) included ‘reduction of VTE risk’ as a goal of treatment. Conclusions: There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Clinical challenges in the management of endocrine side effects of immuno-oncological therapies

SummaryGiven the growing use of immune checkpoint inhibitor (ICI) therapy in oncology, the prevalence of endocrine side effects is rapidly increasing. As clinicians are nowadays frequently confronted with these side effects in routine clinical care, awareness, better knowledge of endocrine irAEs and their clinical presentation and diagnosis is crucial for an adequate management. In this short-review we give a compact overview of the recent recommendations for the management of endocrine irAE related to ICIs and highlight difficulties and uncertainties in current clinical practice.