Symptoms, disease severity and treatment of adults with a new diagnosis of severe aortic stenosis

Objective Contemporary data on patients with previously undiagnosed severe aortic stenosis (AS) are scarce. We aimed to address this gap by gathering data from consecutive patients diagnosed with severe AS on echocardiography. Methods This was a prospective, multicentre, multinational, registry in 23 tertiary care hospitals across 9 European countries. Patients with a diagnosis of severe AS were included using echocardiography (aortic valve area (AVA) <1 cm 2, indexed AVA <0.6 cm 2 /m 2, maximum jet-velocity (V max) >4 m/s and/or mean transvalvular gradient >40 mm Hg). Results The 2171 participants had a mean age of 77.9 years and 48.0% were female. The mean AVA was 0.73 cm 2, V max 4.3 m/s and mean gradient 47.1 mm Hg; 62.1% had left ventricular hypertrophy and 27.3% an ejection fraction (EF) <50%. 1743 patients (80.3%) were symptomatic (shortness-of-breath 91.0%; dizziness 30.2%, chest pain 28.9%). Patients had a EuroSCORE II of 4.0; 25.3% had a creatinine clearance <50 mL/min, and 3.2% had an EF <30%. Symptomatic patients were older and had more comorbidities than asymptomatic patients. Despite European Society of Cardiology 2017 valvular heart disease guideline class I recommendation, in only 76.2% a decision was made for an intervention (transcatheter 50.4%, surgical aortic valve replacement 25.8%). In asymptomatic patients, 57.7% with a class I/IIa indication were scheduled for a procedure, while 36.3% patients without an indication had their valve replaced. Conclusions The majority of patients with severe AS presented at an advanced disease stage. Management of severe AS remained suboptimal in a significant proportion of contemporary patients with severe AS. Trial registration number NCT02241447;Results

Multimodal prehabilitation for major surgery in elderly patients to lower complications: protocol of a randomised, prospective, multicentre, multidisciplinary trial (PREHABIL Trial).

INTRODUCTION The global volume of surgery is growing and the population ageing, and economic pressure is rising. Major surgery is associated with relevant morbidity and mortality. Postoperative reduction in physiological and functional capacity is especially marked in the elderly, multimorbid patient with low fitness level, sarcopenia and malnutrition. Interventions aiming to optimise the patient prior to surgery (prehabilitation) may reduce postoperative complications and consequently reduce health costs. METHODS AND ANALYSIS This is a multicentre, multidisciplinary, prospective, 2-arm parallel-group, randomised, controlled trial with blinded outcome assessment. Primary outcome is the Comprehensive Complications Index at 30 days. Within 3 years, we aim to include 2×233 patients with a proven fitness deficit undergoing major surgery to be randomised using a computer-generated random numbers and a minimisation technique. The study intervention consists of a structured, multimodal, multidisciplinary prehabilitation programme over 2-4 weeks addressing deficits in physical fitness and nutrition, diabetes control, correction of anaemia and smoking cessation versus standard of care. ETHICS AND DISSEMINATION The PREHABIL trial has been approved by the responsible ethics committee (Kantonale Ethikkomission Bern, project ID 2020-01690). All participants provide written informed consent prior to participation. Participant recruitment began in February 2022 (10 and 8 patients analysed at time of submission), with anticipated completion in 2025. Publication of the results in peer-reviewed scientific journals are expected in late 2025. TRIAL REGISTRATION NUMBER NCT04461301

Just Caring: Parsimonious Care in Certain Uncertain Circumstances

Uncertainty is a Hydra-headed phenomenon in health care. From a physician’s perspective there often is uncertainty (many degrees) with respect to diagnosis (and the reliability of the technologies needed to establish a diagnosis), prognosis (and the infinite variety of genetic, physiological, pharmacological, behavioral, technological, economic, and cultural factors that affect the outcome of prognostic judgments), the appropriateness of a therapeutic intervention (perhaps related to medical disagreement), the likely effectiveness of a therapeutic intervention, the risk/ benefit ratio of a therapeutic intervention (potentially complicated by co-morbid conditions), the likelihood of a patient complying with the behaviors needed to maximize the likelihood of a therapeutic outcome, the applicability of a clinical guideline to this patient in the clinic, the reliability of the evidence and research behind that guideline, and, finally, the sheer randomness of natural events at various levels in the health care encounter. That is the background for this presentation. Our question, however, is this: How should all this uncertainty be addressed in the economic/ political context of having to do health care rationing, and in the ethical context of having to do that rationing justly? Today there is an increasing emphasis on the obligation of physicians to provide parsimonious care, i.e., the prudent and cost-effective use of health care resources in caring for individual patients. To focus discussion I offer several common examples, such as $100,000 precision cancer drugs,$40,000 implantable cardiac defibrillators, PCSK9s for lowering “bad” cholesterol, access to ICU beds---- all of which represent uncertain benefit at very great cost. DRGs as a hospital payment mechanism are part of the same problem since they can motivate “premature” discharge of a patient, thereby putting them at uncertain risk for an otherwise avoidable bad health outcome. If physicians cooperate with the intent of DRGs (or other care protocols intended to promote parsimonious care), are they treating their patients unjustly? Must physicians be virtually certain that no harm will come to their patients in order to be just and justified in carrying out parsimonious protocols? “No” is the response I will defend. If a patient does not have a just claim to some health care resource, then the harm that “might” befall them as a result of that denial is properly regarded as being unfortunate but not unjust. Access to health care resources is about access to a limited common good. This is what makes such access a matter of justice rather than a matter of informed consent wherein a patient weighs from their point of view the risks and benefits (and related uncertainty) they are willing to trade off. Matters of justice require social decisions. Patients do not have a presumptive just claim to a $100,000 cancer drug if there is only a small chance that drug would yield an extra six months of life. What level of certainty would generate such a just claim? There is no objectively correct answer to that question. It needs to be resolved, I will argue, through a process of rational democratic deliberation, the results of which will be just and legitimate for all in the relevant clinical circumstances

Management of patients with severe aortic stenosis in the TAVI-era: How recent recommendations are translated into clinical practice

Objective Approximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR. Methods Participants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR. Results Of 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; p<0.001) below the study median; or with a left ventricular end systolic diameter above the study median (p=0.007) were more likely to be assigned to AVR. Conclusions There may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption

Screening for frailty: older populations and older individuals

The concept of frailty as a health dimension in old age is recent and has its origin in the development of geriatric medicine. Initially an unformulated clinical intuition, it is now defined by a diminished physiological reserve of multiple organs that exposes older individuals to increased vulnerability to stressors and a higher risk of adverse outcomes. The operational definition of frailty, however, is still debated. From a diversity of models, two emerged in the early 2000s from epidemiological studies conducted in large population-based aging cohorts. The body of research emphasized prospective associations between a frailty phenotype and a range of adverse outcomes or between a frailty index measuring the accumulation of deficits and death. A few studies showed promising spontaneous remissions in the early stages of frailty, raising expectations for effective interventions. Transitions between frailty stages and effective interventions on frailty nevertheless remain two fields needing further investigation. More recently, these tools have been applied as screening instruments in clinical settings to guide individual decision-making and orient treatments. New questions are raised by the use of instruments developed to screen frailty in epidemiological research for assessing individual situations. Inquiring whether frailty screening is relevant opens a Pandora’s box of doubts and debates. There are many reasons to screen for frailty both from a public health and a clinical perspective that are only exacerbated by the current demographic evolution. Open questions remain about the feasibility of frailty screening, the properties of screening tools, the relevance of an integration of socioeconomic dimensions into screening tools, and the effectiveness of interventions targeting frailty. Fifteen years after the publication of the Fried and Rockwood landmark papers proposing operational definitions of frailty, this article presents an overview of current perspectives and issues around frailty screening in populations and in individuals

Evaluation of Services for the Preoperative Assessment and Management of High-Risk Surgical Patients

Outpatient preoperative assessment clinics, such as the physician-led high-risk clinic in a large metropolitan public hospital in South Australia, have been established to assess and manage surgical patients at high risk of morbidity and mortality due to their medical co-morbidities. To date, the design and implementation of preoperative medical assessment and management has been heterogeneous, with minimal detail on the actual services provided as part of the intervention. Further, there have been no published studies evaluating the costs and outcomes of physician-led preoperative assessment for patients with modifiable medical co-morbidities prior to elective surgery. Five distinct projects contributed to the main aims of this research: to evaluate the preoperative assessment and management services provided by the physician-led high-risk clinic, and provide recommendations for improvement using an explanatory sequential mixed methods approach. This research represents the first comprehensive evaluation of services for the preoperative assessment and management of high-risk surgical patients. Multiple regression analyses identified nine potentially modifiable medical co-morbidities to be associated with increased length of stay and postoperative complications, supporting the rationale that optimisation of poorly controlled medical co-morbidities prior to surgery could improve postoperative outcomes. The costs and effects of physician-led preoperative assessment and management were evaluated using a propensity score-based approach with retrospective and prospective data. It was found that the clinic reduced the frequency of unnecessary admissions and cancellations but significant uncertainty remained around the effect of the clinic on length of hospital stay, postoperative complications, hospital costs and post-discharge mortality. Supplemental data on a prospective cohort of patients identified preoperative health-related quality of life as a potential unmeasured confounder in the evaluation, with high-risk clinic patients reporting lower mean index scores. Semi-structured interviews with surgeons found that the factors influencing their decision to refer a patient to the high-risk clinic appear to be driven by the aim to manage the uncertainty and risk to the patient regarding surgery and it was seen as a strategy for managing difficult and complex cases. Additionally, the integration of the services provided by the clinic in this study appear to offer additional value in supporting the surgical decision-making process for the surgical team and patient beyond the clinical outcomes, such as managing the patient’s expectations regarding care and assistance after discharge from hospital. Further perspectives from patients and other medical professionals collaborating with the clinic should be explored and would provide further insight into the aspects of care that provide additional value. This evaluation provides a guide to the identification of elective surgical patients who are likely to benefit most from preoperative physician-led medical optimisation and provides clarity on the collaborative care provided by the high-risk clinic and surgical teams in managing complex patients, to inform the assessment of such clinics in Australia. Such models of care involving the management of high-risk patients are increasingly likely as the public hospital system is subjected to increasing demands from an ageing population. This research has demonstrated the need to plan for the robust evaluation of new health service initiatives, which may be facilitated through better co-ordinated planning and evaluation across Australian hospitals.Thesis (Ph.D.) -- University of Adelaide, School of Public Health, 201

Evaluation of the impact of the GRACE risk score on the management and outcome of patients hospitalised with non-ST elevation acute coronary syndrome in the UK: protocol of the UKGRIS cluster-randomised registry-based trial

Introduction For non-ST-segment elevation acute coronary syndrome (NSTEACS) there is a gap between the use of class 1 guideline recommended therapies and clinical practice. The GRACE risk score is recommended in international guidelines for the risk stratification of NSTEACS, but its impact on adherence to guideline-indicated treatments and reducing adverse clinical outcomes is unknown. The objective of the UKGRIS trial is to assess the effectiveness of the GRACE risk score tool and associated treatment recommendations on the use of guideline-indicated care and clinical outcomes. Methods and Analysis The UK GRACE Risk Score Intervention Study (UKGRIS), a parallel-group cluster randomised registry-based controlled trial, will allocate hospitals in a 1:1 ratio to manage NSTEACS by standard care or according to the GRACE risk score and associated international guidelines. UKGRIS will recruit a minimum of 3000 patients from at least 30 English National Health Service hospitals and collect healthcare data from national electronic health records. The co-primary endpoints are the use of guideline-indicated therapies, and the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospitalisation or cardiovascular readmission at 12 months. Secondary endpoints include duration of inpatient hospital stay over 12 months, EQ-5D-5L responses and utilities, unscheduled revascularisation and the components of the composite endpoint over 12 months follow-up. Ethics and Dissemination The study has ethical approval (North East - Tyne & Wear South Research Ethics Committee ref: 4/NE/1180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder’s open access policy. Registration ISRCTN29731761, registered 12th January 2017

Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection. The alteplase dose assessment for Pleural infection Therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22–58] to 16% [8–31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247–2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pl