Abstract There is a need to identify patients with an increased risk of dying after acute myocardial infarction (AMI), because sudden cardiac death (SCD) and potentially fatal ventricular tachyarrhythmias can be prevented by an implantable cardioverter-defibrillator, or in some cases, with aggressively optimized drug or revascularization therapy. The present study was designed to study the predictive power of non-invasive risk markers and all-cause, cardiac and arrhythmic mortality in 700 consecutive post-AMI patients discharged alive with optimal medication according to contemporary guidelines. Detrended fluctuation analysis of heart rate variability (HRV) predicted all-cause mortality beyond clinical variables as well as left ventricular function in post-AMI patients. The predictive power of the short-term scaling exponent α1 was higher than that of the traditional indexes of HRV (for α1 < 0.65, the risk ratio (RR) in multivariate analysis was 5.1, with 95% confidence intervals (CI) 2.9-8.9; p < 0.001). HRV results from a conventional 24-hour electrocardiographic (ECG) recording system differed significantly when compared to a system with a higher sampling frequency. The difference was generally more pronounced in post-AMI patients than in healthy subjects. The presence of sustained T-wave alternans during a predischarge exercise test after AMI was not a marker of mortality. However, the inability to perform an exercise test or to reach the heart rate of 105 beats/min predicted independently all-cause (RR 9.3, 95% CI 2.0-43.3, p < 0.01) and cardiac mortality (RR 11.1, 95% CI 2.4-50.8, p < 0.01). High levels of natriuretic peptides were associated with both sudden and non-sudden cardiac mortality. B-type natriuretic peptide provided more specific independent information on the risk for subsequent SCD (RR 3.9, 95% CI 1.2-12.3, p < 0.05) than non-SCD. SCDs occurred mainly more than 18 months after AMI, and the proportion of SCD was less than 40% of all cardiac deaths. Common arrhythmia markers such as the presence of ventricular premature beats or episodes of nonsustained ventricular tachycardia during ambulatory recordings, the time domain parameters of HRV, baroreflex sensitivity, QT dispersion and QRS complex duration provided only limited predictive power on the risk of SCD or arrhythmic events in patients with optimized beta-blocking therapy. Many risk variables previously considered to predict SCD were better predictors of non-SCD than SCD. Conclusions: 1. The epidemiological pattern of SCD was different from that reported previously. 2. Many arrhythmia risk markers provided only limited information on the risk of SCD. 3. Short-term fractal scaling exponent α1 provided potentially useful information on the risk for all-cause mortality, and BNP was useful in predicting the risk of SCD in a post-AMI population with optimized therapy.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13259号 / 論医博第2177号 / 新制||医||1037(附属図書館) / (主査)教授 横出 正之, 教授 富樫 かおり, 教授 湊谷 謙司 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Suicide is a significant public health issue in the US. Despite national and international prioritization since 1996, little definitive progress has been made in terms of identification and intervention in cases of elevated suicide risk. Forty percent of those who died by suicide attended an emergency department within a year of death. Therefore, universal suicide risk screening in emergency departments could prove a vital component to a national suicide prevention strategy. The present study empirically evaluated the universal suicide risk screening program recently implemented at Parkland Health and Hospital System. The sample consisted of patients over 18 years of age (N=333,855; Mage=42.7, 32% male) screened as part of routine clinical care from May 4th, 2015, through November 3rd, 2015. The Parkland Algorithm for Suicide Screening (PASS) is part of a clinical decision support system for responses to Columbia - Suicide Severity Rating Scale Clinical Practice Screener (C-SSRS) items, leading to an automated clinical response via three suicide risk stratification levels: no action for no risk identified, psychiatric social worker assessment for moderate risk identified, and psychiatrist/psychologist interview for high risk identified. The present study used receiver operating characteristic (ROC) curve analysis, which found the PASS predicted disposition (z=30.46, p<.001, AUC=.78, CI95=.77, .81). This study also evaluated the cutpoints separating suicide risk stratification and levels of clinical response. The results supported the first cutpoint and highlighted a need for additional data to address the second cutpoint. The results of the present study suggest that the universal suicide risk screening program at Parkland Health and Hospital System is an important step toward addressing suicide prevalence in the US.

Cardiovascular disease is the leading cause of death in women. Although overall mortality from coronary heart disease (CHD) has decreased, there are subsets of patients, particularly youngwomen, in whom the mortality rate has increased. Underlying sex differences in CHD may be an explanation. Women have more frequent symptoms, more ischemia, and higher mortality than men, but less obstructive coronary artery disease (CAD). Despite this, traditional risk factor assessment has been ineffective in risk stratifying women, prompting the emergence of novel markers and prediction scores to identify a population at risk. Sex differences inmanifestations and the pathophysiology of CHD also have led to differences in the selection of diagnostic testing and treatment options for women, having profound effects on outcomes. The frequent finding of nonobstructive CAD in women with ischemia suggests microvascular dysfunction as an underlying cause; therefore, coronary reactivity and endothelial function testing may add to diagnostic accuracy in female patients. In spite of evidence that women benefit from the same therapies as men, they continue to receive lessaggressive therapy, which is reflected in higher healthcare resource utilization and adverse outcomes. More sex-specific research is needed in the area of symptomatic nonobstructive CAD to define the optimal therapeutic approach.

Cardiovascular disease is the leading cause of death in women. Although overall mortality from coronary heart disease (CHD) has decreased, there are subsets of patients, particularly youngwomen, in whom the mortality rate has increased. Underlying sex differences in CHD may be an explanation. Women have more frequent symptoms, more ischemia, and higher mortality than men, but less obstructive coronary artery disease (CAD). Despite this, traditional risk factor assessment has been ineffective in risk stratifying women, prompting the emergence of novel markers and prediction scores to identify a population at risk. Sex differences inmanifestations and the pathophysiology of CHD also have led to differences in the selection of diagnostic testing and treatment options for women, having profound effects on outcomes. The frequent finding of nonobstructive CAD in women with ischemia suggests microvascular dysfunction as an underlying cause; therefore, coronary reactivity and endothelial function testing may add to diagnostic accuracy in female patients. In spite of evidence that women benefit from the same therapies as men, they continue to receive lessaggressive therapy, which is reflected in higher healthcare resource utilization and adverse outcomes. More sex-specific research is needed in the area of symptomatic nonobstructive CAD to define the optimal therapeutic approach.

No description available.

<p><strong>Background:</strong> Syncope is estimated to account for 1% to 3% of emergency department (ED) annual visits in North America. Although most potential causes of syncope are benign and self-limited, others are associated with serious morbidity and substantial mortality. Recent efforts have focused on prospective identification of ED patients with syncope who are at high risk for early serious adverse outcomes in an attempt to hospitalize them at their first visit to the ED.</p> <p><strong>Objective: </strong>The purpose of this thesis is to describe the methodological issues related to the design of a study to determine whether the Revised Strategy of Syncope Diagnosis in the Emergency Room at the General Hospital Structured Care Pathway (RESASTER-SCP) is superior to usual care in identifying patients at low risk for serious adverse outcomes presenting to the ED who can be safely discharged home. <strong></strong></p> <p><strong>Design and Methods: </strong>A cluster randomized trial will be conducted with EDs (16 teaching and 46 non-teaching general hospitals) as the unit of randomization and patients presenting with syncope (TLOC) as the unit of analysis. Study participants will be followed at 1, 3, 5, and 12 months after the intervention (RESASTER-SCP vs. usual care) has been applied in the ED. Intention to treat analysis will be used. The analysis will be conducted at the individual level using proportions. Alpha level will be set at 0.05 with a power of 0.80 for the primary outcome.<strong></strong></p> <p><strong>Conclusion: </strong>This thesis describes some of the methodological issues concerning the design of a cluster randomized trial to determine whether or not RESASTER-SCP is superior to usual care in identifying patients presenting with syncope to the ED who can be safely discharged home.</p> / Master of Science (MSc)

<p><strong>Background: </strong>Myocardial injury after noncardiac surgery (MINS) increases the risk of 30-day mortality. Intraoperative hemodynamic events (i.e., tachycardia, bradycardia, hypotension, and hypertension) may contribute to developing MINS.</p> <p><strong>Objectives: </strong>To determine if the addition of the duration spent within predefined intraoperative systolic blood pressure (BP; mmHg) (i.e.,160-199 and ≥200) and heart rate (HR; bpm) (i.e.,100-140 and >140) hemodynamic bands improved the prediction of Day 1 MINS (i.e., postoperative troponin T elevation ≥0.03 ng/ml within the first day after surgery) beyond preoperative risk model prediction.</p> <p><strong>Methods: </strong> Prospective observational data was used to developed a baseline risk model to predict Day 1 MINS. Preoperative HR, systolic BP, and hemoglobin as well as intraoperative duration spent within each predefined hemodynamic band were explored to identify optimal thresholds for the prediction of Day-1 MINS. Preoperative variables were added to the baseline risk model to create a preoperative model. Intraoperative variables were then added to the preoperative risk model to create the final model. Models were compared using discrimination (c-statistic) and net reclassification index (NRI).</p> <p><strong>Results: </strong>Adding preoperative hemoglobin ≤105 g/dL, systolic BP110 improved baseline model discrimination (0.783 to 0.792, p5min; HR >100 for >147min; systolic BP59min and systolic BP >160 for >42min further improved discrimination (0.8; p</p> <p><strong>Conclusion:</strong> Adding intraoperative hemodynamic durations significantly improved Day-1 MINS model discrimination and risk stratification compared to the baseline risk model.</p> / Master of Health Sciences (MSc)

Background: The cumulative effect of taking anticholinergic medicines (anticholinergic burden) is associated with adverse outcomes for older people. Prevalence of anticholinergic prescribing is increasing, and there is a need for tools to proactively identify at-risk patients for medication reviews. Aim: To explore the need for, and feasibility of, an integrated case-finding tool that predicts risks using electronic health records (EHRs), facilitating the review of anticholinergic medicines for frail older people. Methods: Mixed methods, adopting a pragmatic approach. A systematic review, prediction modelling of cohort study data, and qualitative interviews were undertaken. Results: The systematic review found anticholinergic exposure was associated with adverse outcomes for the frail; poorer physical function, falls, and mortality, indicating a need for a risk reducing intervention. In the prediction modelling study, predicting risks using composite measures of anticholinergic burden and frailty indicated limited feasibility. Neither enhanced the performance of best subset models using cohort study data. Their predictive utility needs to be investigated using EHR data, to determine their feasibility within primary care. The qualitative study found healthcare professionals needed a proactive tool, supporting risk prediction as a feasible approach. Factors influencing future implementation were; upskilling requirements, deprescribing confidence, patient reluctance, motivation, holistic care, interoperability, trust in risk prediction, remuneration, among other barriers and facilitators. Conclusions: Through identifying a need, and potential feasibility, foundations towards the future developments of a case-finding tool have been provided, informing an early tool prototype (AC-FRAIL). Recommendations for further work suggest a roadmap ahead, to maximise the potential for integrated solutions to proactively reduce anticholinergic risks. / NIHR Yorkshire and Humber Patient Safety Translational Research Centre (NIHR YHPSTRC)

Yes / Introduction: Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials. Methods and analysis: WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches. Ethics and dissemination: The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities. / This work was supported by NIHR Programme Grants for Applied Research (grant number: NIHR202862).