Academic literature on the topic 'Major Adverse Clinical Event (MACE)'

AbstractPatient safety is a fundamental principle of health care. However, many medical practices and risks associated with health care are emerging as major challenges for patient safety globally and contribute significantly to the burden of harm due to unsafe care. Available evidence suggests hospitalizations in low- and middle-income countries lead annually to 134 million adverse events, contributing to 2.6 million deaths. About 134 million adverse events worldwide give rise to 2.6 million deaths every year. Estimates indicate that in high-income countries, about 1 in 10 patients is harmed while receiving hospital care. This problem affects both high-income countries and low- and middle countries even if priorities and issues may differ. The most important adverse events concern medication procedures, healthcare-associated infections, surgical procedures, injection safety, blood transfusions, venous thromboembolism, sepsis, and diagnostic and radiation errors. Since 1999 when the Institute of Medicine (IOM) published its report “To err is human,” some progress has been made but patient harm is still a daily problem in healthcare. As a matter of fact, new threats are emerging due to population aging, along with new treatments and technologies which must be dealt with in addition to still-unresolved, long-standing problems. In this context, it is very important to adopt an international common strategy that creates networks, shares knowledge, programs, tools, good practices and develop and track indicators focusing on the specific priorities of each country and region.

Myocardial infarction (MI) continues to be a major contributor to global cardiovascular morbidity and mortality, despite advancements in revascularization techniques such as percutaneous coronary intervention (PCI). Recent attention has shifted toward evaluating the autonomic nervous system (ANS) as a key determinant of post-infarction prognosis. Heart rate variability (HRV), a non-invasive marker of autonomic regulation, has emerged as a sensitive tool for assessing cardiac autonomic dysfunction and stratifying cardiovascular risk following MI. Decreased HRV—particularly reductions in time-domain parameters such as standard deviation of normal RR intervals (SDNN) and the root mean square of successive RR interval differences (RMSSD), and altered low-frequency/high-frequency (LF/HF) ratios—has been consistently associated with increased incidence of arrhythmias, major adverse cardiovascular events (MACE), and mortality in both acute and long-term settings. Studies indicate that early reperfusion improves HRV indices, reflecting restored autonomic balance, whereas persistent HRV impairment signals poor prognosis even after successful PCI. Furthermore, advancements in wearable technologies and artificial intelligence have enabled real-time HRV monitoring, expanding its clinical applicability. Incorporating HRV into conventional risk assessment models may enhance the identification of high-risk patients and guide individualized therapeutic strategies. This chapter reviews the physiological underpinnings, measurement methods, clinical relevance, and prognostic value of HRV in the context of MI, with a focus on its potential as an integrative tool in future cardiovascular care.

Based on an understanding of how a stenosis impacts the ability of a coronary artery to deliver adequate myocardial blood flow, coupled with the results of the DEFER, FAME, and FAME 2 studies, fractional flow reserve (FFR) has become the most widely used and the only guideline-recommended method for the invasive functional evaluation of patients with stable ischaemic heart disease. The absolute value of FFR predicts prognosis and when treatment decisions are made or modified in response to the FFR value, clinical outcomes are improved. Major adverse cardiovascular event rates related to lesions deferred for revascularization on the basis of non-ischaemic FFR results are low. When compared to FFR, resting (non-hyperaemic) indices of physiological stenosis severity such as resting Pd/Pa or instantaneous wave-free ratio are associated with misclassification of 20% of lesions using binary cut-off values and 10% of lesions when hybrid strategies are used. Nevertheless, in low-risk patient populations, randomized clinical trials comparing instantaneous wave-free ratio versus FFR-guided management have shown non-inferiority. A comprehensive invasive assessment of patients with stable ischaemic heart disease requires an evaluation of microvascular dysfunction most commonly obtained by measuring the index of microcirculatory resistance. Patients with non-ischaemic FFR values but an elevated index of microcirculatory resistance have an increased incidence of adverse events.

Abstract Antithrombotic strategies in primary cardiovascular prevention essentially revolve around the use of aspirin. This chapter provides an update and guidance for the use of aspirin in patients without previous clinical evidence of vascular disease. In contrast to secondary prevention, aspirin in primary prevention is widely debated in part because early trials predated the statin era. furthermore, because prevention of cardiovascular outcomes demonstrated in several trials was counterbalanced by increased risk for bleeding, a net clinical benefit has not clearly been shown in pooled estimates. Using data from the most recent trials, and performing a meta-regression of benefits and risks associated with aspirin use as related to the 10-year risk of major adverse cardiovascular events (MACEs), a tailored approach to aspirin prescription in primary prevention is proposed. In patients aged less than 70 years with optimal risk factor control, individual cardiovascular risk should be carefully evaluated, while also considering bleeding risk and patient preferences. Absolute MACE reduction appears superior to the hazard of haemorrhagic events in patients at intermediate–high cardiovascular risk without a prohibitive bleeding risk, and this category of individuals, as well as those with documented evidence of subclinical carotid, coronary, or peripheral atherosclerotic vascular disease, appear to be a proper target population. Treatment of other cardiovascular risk factors, such as high cholesterol, should, however, be prioritized prior to aspirin administration, and this should be accompanied, especially in the elderly, by the concurrent administration of gastroprotective agents.

Cardiovascular disease (CVD) is one of the major causes of death all over the world and the mortality rate is higher than other causes. Hence, we propose a novel deep neural network (DNN)-based prediction model for the major adverse cardiovascular event (MACE) occurrences in patients with non-ST-Elevation myocardial infarction (NSTEMI) to improve the prediction accuracy of CVD. The research contents are described as follows. First, for the experiment, we use the Korean Acute Myocardial Infarction Registry (KAMIR-NIH) dataset with 2 years follow-ups and then preprocess the extracted data, such as processing the missing values, solving the imbalance problem, and applying the normalization meth to scale all the datasets in the same range for the experiment. Then we design a DNN-based prognosis model for the occurrences of MACE in NSTEMI patients. Finally, we evaluate the proposed model’s performance and compare it with several applied machine learning algorithms, such as logistic regression, K-Nearest Neighbors, decision tree, and support vector machine. The result shows that the performance of our proposed method outperformed other machine learning-based prediction models.

Managing adverse incidents1110 Fire safety1112 Missing and absconding patients1113 Major incidents1114 Medical device failure1115 Utility failure1116 Violent and aggressive patients1118 Violent and aggressive relatives1120 Control of Substances Hazardous to Health (COSHH)1121 This refers to any event that produces unexpected or unwanted effects involving the safety of a person or the loss or damage of property. Incidents may be clinical, health and safety, security, assaults, or accidents....

The discovery of a new drug usually takes 10-15 years. Within this time period, the candidate drug is thoroughly screened for its beneficial as well as side effects. But the side, adverse or toxic effects cannot be detected to a full scale due to some special reasons. The beneficial effects and toxicity of new drugs and vaccines are usually studied by “Clinical trials”, which are divided into four categories ranging from clinical trial phases I to IV. During clinical trial phase-III, about 4,000-10,000 patients are involved and after passing this phase, the drug is allowed to enter into the global market. Then, billions of people, including those who were excluded in phase-III, may be administered with this drug. It is worthy to mention that these 4,000-10,000 patients may not show many of the side effects or toxic actions. The undetected adverse drug reactions (ADRs) are studied in clinical trial phase-IV, which is also known as post market surveillance. For this reason, the ADRs are compared with the tip of the iceberg, as it indicates the minor part of a major event. This phenomenon gave birth to a new branch of the pharmacology known as Pharmacovigilance.

Adverse Drug Events (ADEs) are currently considered as a major public health issue, endangering patients' safety and causing significant healthcare costs. Several research efforts are currently concentrating on the reduction of preventable ADEs by employing Information Technology (IT) solutions, which aim to provide healthcare professionals and patients with relevant knowledge and decision support tools. In this context, we present a knowledge engineering approach towards the construction of a Knowledge-based System (KBS) regarded as the core part of a CDSS (Clinical Decision Support System) for ADE prevention, all developed in the context of the EU-funded research project PSIP (Patient Safety through Intelligent Procedures in Medication). In the current paper, we present the knowledge sources considered in PSIP and the implications they pose to knowledge engineering, the methodological approach followed, as well as the components defining the knowledge engineering framework based on relevant state-of-the-art technologies and representation formalisms.

Background: Major depressive disorder is a common mental disorder. Many pressing questions regarding depression treatment and outcomes exist, and new, efficient research approaches are necessary to address them. The primary objective of this project is to demonstrate the feasibility and value of capturing the harmonized depression outcome measures in the clinical workflow and submitting these data to different registries. Secondary objectives include demonstrating the feasibility of using these data for patient-centered outcomes research and developing a toolkit to support registries interested in sharing data with external researchers. Methods: The harmonized outcome measures for depression were developed through a multi-stakeholder, consensus-based process supported by AHRQ. For this implementation effort, the PRIME Registry, sponsored by the American Board of Family Medicine, and PsychPRO, sponsored by the American Psychiatric Association, each recruited 10 pilot sites from existing registry sites, added the harmonized measures to the registry platform, and submitted the project for institutional review board review Results: The process of preparing each registry to calculate the harmonized measures produced three major findings. First, some clarifications were necessary to make the harmonized definitions operational. Second, some data necessary for the measures are not routinely captured in structured form (e.g., PHQ-9 item 9, adverse events, suicide ideation and behavior, and mortality data). Finally, capture of the PHQ-9 requires operational and technical modifications. The next phase of this project will focus collection of the baseline and follow-up PHQ-9s, as well as other supporting clinical documentation. In parallel to the data collection process, the project team will examine the feasibility of using natural language processing to extract information on PHQ-9 scores, adverse events, and suicidal behaviors from unstructured data. Conclusion: This pilot project represents the first practical implementation of the harmonized outcome measures for depression. Initial results indicate that it is feasible to calculate the measures within the two patient registries, although some challenges were encountered related to the harmonized definition specifications, the availability of the necessary data, and the clinical workflow for collecting the PHQ-9. The ongoing data collection period, combined with an evaluation of the utility of natural language processing for these measures, will produce more information about the practical challenges, value, and burden of using the harmonized measures in the primary care and mental health setting. These findings will be useful to inform future implementations of the harmonized depression outcome measures.

Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4

Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4

Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4

Abstract Rationale Early treatment of asthma exacerbations with inhaled corticosteroids is the best strategy for management, although use of an increased or stable dose is questioned. Objectives To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids as part of a patient-initiated action plan for the home management of exacerbations in children and adults with persistent asthma. Search methods We searched the Cochrane Airways Group Specialised Register (part of CENTRAL), MEDLINE, Embase, CINAHL, major trials registries and handsearched abstracts up to 20 December 2021. Eligibility criteria Parallel and cross-over blinded randomised controlled trials (RCTs) Outcomes Treatment failure (the need for rescue oral steroids) in the randomised population and in the subset who initiated the study inhaler, unscheduled physician visits, unscheduled acute care, emergency department or hospital visits, serious and non-serious adverse events, and duration of exacerbation. Risk of bias We used Risk of Bias 2 (RoB 2)and the tool's extension for cross-over trials. Synthesis methods We conducted meta-analyses using fixed-effect models to calculate odds ratios (OR) and 95% confidence intervals (CI) for all but one outcome, which used random-effects models due to heterogeneity (treatment failure in the subset who initiated the study inhaler). We summarised certainty of evidence according to GRADE methods. Included studies We included nine RCTs (seven parallel and two cross‐over) with a total of 1923 participants. The studies were conducted in Europe, North America, and Australasia and were published between 1998 and 2018. Five studies evaluated adult populations (1247 participants; ≥ 15 years), and four studies evaluated child or adolescent populations (676 participants; < 15 years). Approximately 50% of randomised participants initiated the study inhaler (range 23% to 100%). The studies reported treatment failure in various ways, so we made assumptions to allow us to combine data. Synthesis of results People randomised to increase their inhaled corticosteroids dose at the first signs of an exacerbation probably had similar odds of needing rescue oral corticosteroids to those randomised to a placebo inhaler (OR 0.97, 95% CI 0.76 to 1.25; 8 studies, 1774 participants; moderate-certainty evidence). Results for the same outcome in the subset of participants who initiated the study inhaler (approximately 50%) gives a different point estimate with very low certainty due to heterogeneity, imprecision and risk of bias (OR 0.84, 95% CI 0.54 to 1.30; 7 studies, 766 participants; random-effects model used). For adverse effects, imprecision and risk of bias from missing data, outcome measurement and reporting meant we were very uncertain about the effect estimate (serious adverse events OR 1.69, 95% CI 0.77 to 3.71; 2 studies, 394 participants; non-serious adverse events OR 2.15, 95% CI 0.68 to 6.73; 2 studies, 142 participants). We had very low confidence in the effect estimates for unscheduled physician visits, unscheduled acute care, emergency department or hospital visits and duration of exacerbation due to risk of bias. Authors' conclusions Evidence suggests that adults and children with mild to moderate asthma are unlikely to have an important reduction in the need for oral steroids from increasing a patient's inhaled corticosteroid dose at the first sign of an exacerbation. Other clinically important benefits and potential harms cannot be ruled out due to wide confidence intervals, risk of bias in the studies, and assumptions made for synthesis when combining data. Included studies reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. Differences between the blinded and unblinded studies should be investigated. Funding This Cochrane Review had no dedicated funding. Registration Protocol (2009): doi.org/10.1002/14651858.CD007524 Original review (2010): doi.org/10.1002/14651858.CD007524.pub3 Review update (2014): doi.org/10.1002/14651858.CD007524.pub4

Background Lung cancer is the number one cause of cancer death worldwide.(1) It is the fifth most commonly diagnosed cancer in Australia (12,741 cases diagnosed in 2018) and the leading cause of cancer death.(2) The number of years of potential life lost to lung cancer in Australia is estimated to be 58,450, similar to that of colorectal and breast cancer combined.(3) While tobacco control strategies are most effective for disease prevention in the general population, early detection via low dose computed tomography (LDCT) screening in high-risk populations is a viable option for detecting asymptomatic disease in current (13%) and former (24%) Australian smokers.(4) The purpose of this Evidence Check review is to identify and analyse existing and emerging evidence for LDCT lung cancer screening in high-risk individuals to guide future program and policy planning. Evidence Check questions This review aimed to address the following questions: 1. What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? 2. What is the evidence of potential harms from lung cancer screening for higher-risk individuals? 3. What are the main components of recent major lung cancer screening programs or trials? 4. What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Summary of methods The authors searched the peer-reviewed literature across three databases (MEDLINE, PsycINFO and Embase) for existing systematic reviews and original studies published between 1 January 2009 and 8 August 2019. Fifteen systematic reviews (of which 8 were contemporary) and 64 original publications met the inclusion criteria set across the four questions. Key findings Question 1: What is the evidence for the effectiveness of lung cancer screening for higher-risk individuals? There is sufficient evidence from systematic reviews and meta-analyses of combined (pooled) data from screening trials (of high-risk individuals) to indicate that LDCT examination is clinically effective in reducing lung cancer mortality. In 2011, the landmark National Lung Cancer Screening Trial (NLST, a large-scale randomised controlled trial [RCT] conducted in the US) reported a 20% (95% CI 6.8% – 26.7%; P=0.004) relative reduction in mortality among long-term heavy smokers over three rounds of annual screening. High-risk eligibility criteria was defined as people aged 55–74 years with a smoking history of ≥30 pack-years (years in which a smoker has consumed 20-plus cigarettes each day) and, for former smokers, ≥30 pack-years and have quit within the past 15 years.(5) All-cause mortality was reduced by 6.7% (95% CI, 1.2% – 13.6%; P=0.02). Initial data from the second landmark RCT, the NEderlands-Leuvens Longkanker Screenings ONderzoek (known as the NELSON trial), have found an even greater reduction of 26% (95% CI, 9% – 41%) in lung cancer mortality, with full trial results yet to be published.(6, 7) Pooled analyses, including several smaller-scale European LDCT screening trials insufficiently powered in their own right, collectively demonstrate a statistically significant reduction in lung cancer mortality (RR 0.82, 95% CI 0.73–0.91).(8) Despite the reduction in all-cause mortality found in the NLST, pooled analyses of seven trials found no statistically significant difference in all-cause mortality (RR 0.95, 95% CI 0.90–1.00).(8) However, cancer-specific mortality is currently the most relevant outcome in cancer screening trials. These seven trials demonstrated a significantly greater proportion of early stage cancers in LDCT groups compared with controls (RR 2.08, 95% CI 1.43–3.03). Thus, when considering results across mortality outcomes and early stage cancers diagnosed, LDCT screening is considered to be clinically effective. Question 2: What is the evidence of potential harms from lung cancer screening for higher-risk individuals? The harms of LDCT lung cancer screening include false positive tests and the consequences of unnecessary invasive follow-up procedures for conditions that are eventually diagnosed as benign. While LDCT screening leads to an increased frequency of invasive procedures, it does not result in greater mortality soon after an invasive procedure (in trial settings when compared with the control arm).(8) Overdiagnosis, exposure to radiation, psychological distress and an impact on quality of life are other known harms. Systematic review evidence indicates the benefits of LDCT screening are likely to outweigh the harms. The potential harms are likely to be reduced as refinements are made to LDCT screening protocols through: i) the application of risk predication models (e.g. the PLCOm2012), which enable a more accurate selection of the high-risk population through the use of specific criteria (beyond age and smoking history); ii) the use of nodule management algorithms (e.g. Lung-RADS, PanCan), which assist in the diagnostic evaluation of screen-detected nodules and cancers (e.g. more precise volumetric assessment of nodules); and, iii) more judicious selection of patients for invasive procedures. Recent evidence suggests a positive LDCT result may transiently increase psychological distress but does not have long-term adverse effects on psychological distress or health-related quality of life (HRQoL). With regards to smoking cessation, there is no evidence to suggest screening participation invokes a false sense of assurance in smokers, nor a reduction in motivation to quit. The NELSON and Danish trials found no difference in smoking cessation rates between LDCT screening and control groups. Higher net cessation rates, compared with general population, suggest those who participate in screening trials may already be motivated to quit. Question 3: What are the main components of recent major lung cancer screening programs or trials? There are no systematic reviews that capture the main components of recent major lung cancer screening trials and programs. We extracted evidence from original studies and clinical guidance documents and organised this into key groups to form a concise set of components for potential implementation of a national lung cancer screening program in Australia: 1. Identifying the high-risk population: recruitment, eligibility, selection and referral 2. Educating the public, people at high risk and healthcare providers; this includes creating awareness of lung cancer, the benefits and harms of LDCT screening, and shared decision-making 3. Components necessary for health services to deliver a screening program: a. Planning phase: e.g. human resources to coordinate the program, electronic data systems that integrate medical records information and link to an established national registry b. Implementation phase: e.g. human and technological resources required to conduct LDCT examinations, interpretation of reports and communication of results to participants c. Monitoring and evaluation phase: e.g. monitoring outcomes across patients, radiological reporting, compliance with established standards and a quality assurance program 4. Data reporting and research, e.g. audit and feedback to multidisciplinary teams, reporting outcomes to enhance international research into LDCT screening 5. Incorporation of smoking cessation interventions, e.g. specific programs designed for LDCT screening or referral to existing community or hospital-based services that deliver cessation interventions. Most original studies are single-institution evaluations that contain descriptive data about the processes required to establish and implement a high-risk population-based screening program. Across all studies there is a consistent message as to the challenges and complexities of establishing LDCT screening programs to attract people at high risk who will receive the greatest benefits from participation. With regards to smoking cessation, evidence from one systematic review indicates the optimal strategy for incorporating smoking cessation interventions into a LDCT screening program is unclear. There is widespread agreement that LDCT screening attendance presents a ‘teachable moment’ for cessation advice, especially among those people who receive a positive scan result. Smoking cessation is an area of significant research investment; for instance, eight US-based clinical trials are now underway that aim to address how best to design and deliver cessation programs within large-scale LDCT screening programs.(9) Question 4: What is the cost-effectiveness of lung cancer screening programs (include studies of cost–utility)? Assessing the value or cost-effectiveness of LDCT screening involves a complex interplay of factors including data on effectiveness and costs, and institutional context. A key input is data about the effectiveness of potential and current screening programs with respect to case detection, and the likely outcomes of treating those cases sooner (in the presence of LDCT screening) as opposed to later (in the absence of LDCT screening). Evidence about the cost-effectiveness of LDCT screening programs has been summarised in two systematic reviews. We identified a further 13 studies—five modelling studies, one discrete choice experiment and seven articles—that used a variety of methods to assess cost-effectiveness. Three modelling studies indicated LDCT screening was cost-effective in the settings of the US and Europe. Two studies—one from Australia and one from New Zealand—reported LDCT screening would not be cost-effective using NLST-like protocols. We anticipate that, following the full publication of the NELSON trial, cost-effectiveness studies will likely be updated with new data that reduce uncertainty about factors that influence modelling outcomes, including the findings of indeterminate nodules. Gaps in the evidence There is a large and accessible body of evidence as to the effectiveness (Q1) and harms (Q2) of LDCT screening for lung cancer. Nevertheless, there are significant gaps in the evidence about the program components that are required to implement an effective LDCT screening program (Q3). Questions about LDCT screening acceptability and feasibility were not explicitly included in the scope. However, as the evidence is based primarily on US programs and UK pilot studies, the relevance to the local setting requires careful consideration. The Queensland Lung Cancer Screening Study provides feasibility data about clinical aspects of LDCT screening but little about program design. The International Lung Screening Trial is still in the recruitment phase and findings are not yet available for inclusion in this Evidence Check. The Australian Population Based Screening Framework was developed to “inform decision-makers on the key issues to be considered when assessing potential screening programs in Australia”.(10) As the Framework is specific to population-based, rather than high-risk, screening programs, there is a lack of clarity about transferability of criteria. However, the Framework criteria do stipulate that a screening program must be acceptable to “important subgroups such as target participants who are from culturally and linguistically diverse backgrounds, Aboriginal and Torres Strait Islander people, people from disadvantaged groups and people with a disability”.(10) An extensive search of the literature highlighted that there is very little information about the acceptability of LDCT screening to these population groups in Australia. Yet they are part of the high-risk population.(10) There are also considerable gaps in the evidence about the cost-effectiveness of LDCT screening in different settings, including Australia. The evidence base in this area is rapidly evolving and is likely to include new data from the NELSON trial and incorporate data about the costs of targeted- and immuno-therapies as these treatments become more widely available in Australia.