A hybrid decision support model to discover informative knowledge in diagnosing acute appendicitis

BACKGROUND: The aim of this study is to develop a simple and reliable hybrid decision support model by combining statistical analysis and decision tree algorithms to ensure high accuracy of early diagnosis in patients with suspected acute appendicitis and to identify useful decision rules. METHODS: We enrolled 326 patients who attended an emergency medical center complaining mainly of acute abdominal pain. Statistical analysis approaches were used as a feature selection process in the design of decision support models, including the Chi-square test, Fisher's exact test, the Mann-Whitney U-test (p < 0.01), and Wald forward logistic regression (entry and removal criteria of 0.01 and 0.05, or 0.05 and 0.10, respectively). The final decision support models were constructed using the C5.0 decision tree algorithm of Clementine 12.0 after pre-processing. RESULTS: Of 55 variables, two subsets were found to be indispensable for early diagnostic knowledge discovery in acute appendicitis. The two subsets were as follows: (1) lymphocytes, urine glucose, total bilirubin, total amylase, chloride, red blood cell, neutrophils, eosinophils, white blood cell, complaints, basophils, glucose, monocytes, activated partial thromboplastin time, urine ketone, and direct bilirubin in the univariate analysis-based model; and (2) neutrophils, complaints, total bilirubin, urine glucose, and lipase in the multivariate analysis-based model. The experimental results showed that the model with univariate analysis (80.2%, 82.4%, 78.3%, 76.8%, 83.5%, and 80.3%) outperformed models using multivariate analysis (71.6%, 69.3%, 73.7%, 69.7%, 73.3%, and 71.5% with entry and removal criteria of 0.01 and 0.05; 73.5%, 66.0%, 80.0%, 74.3%, 72.9%, and 73.0% with entry and removal criteria of 0.05 and 0.10) in terms of accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under ROC curve, during a 10-fold cross validation. A statistically significant difference was detected in the pairwise comparison of ROC curves (p < 0.01, 95% CI, 3.13-14.5; p < 0.05, 95% CI, 1.54-13.1). The larger induced decision model was more effective for identifying acute appendicitis in patients with acute abdominal pain, whereas the smaller induced decision tree was less accurate with the test data. CONCLUSIONS: The decision model developed in this study can be applied as an aid in the initial decision making of clinicians to increase vigilance in cases of suspected acute appendicitis

Information technologies for pain management

Millions of people around the world suffer from pain, acute or chronic and this raises the importance of its screening, assessment and treatment. The importance of pain is attested by the fact that it is considered the fifth vital sign for indicating basic bodily functions, health and quality of life, together with the four other vital signs: blood pressure, body temperature, pulse rate and respiratory rate. However, while these four signals represent an objective physical parameter, the occurrence of pain expresses an emotional status that happens inside the mind of each individual and therefore, is highly subjective that makes difficult its management and evaluation. For this reason, the self-report of pain is considered the most accurate pain assessment method wherein patients should be asked to periodically rate their pain severity and related symptoms. Thus, in the last years computerised systems based on mobile and web technologies are becoming increasingly used to enable patients to report their pain which lead to the development of electronic pain diaries (ED). This approach may provide to health care professionals (HCP) and patients the ability to interact with the system anywhere and at anytime thoroughly changes the coordinates of time and place and offers invaluable opportunities to the healthcare delivery. However, most of these systems were designed to interact directly to patients without presence of a healthcare professional or without evidence of reliability and accuracy. In fact, the observation of the existing systems revealed lack of integration with mobile devices, limited use of web-based interfaces and reduced interaction with patients in terms of obtaining and viewing information. In addition, the reliability and accuracy of computerised systems for pain management are rarely proved or their effects on HCP and patients outcomes remain understudied. This thesis is focused on technology for pain management and aims to propose a monitoring system which includes ubiquitous interfaces specifically oriented to either patients or HCP using mobile devices and Internet so as to allow decisions based on the knowledge obtained from the analysis of the collected data. With the interoperability and cloud computing technologies in mind this system uses web services (WS) to manage data which are stored in a Personal Health Record (PHR). A Randomised Controlled Trial (RCT) was implemented so as to determine the effectiveness of the proposed computerised monitoring system. The six weeks RCT evidenced the advantages provided by the ubiquitous access to HCP and patients so as to they were able to interact with the system anywhere and at anytime using WS to send and receive data. In addition, the collected data were stored in a PHR which offers integrity and security as well as permanent on line accessibility to both patients and HCP. The study evidenced not only that the majority of participants recommend the system, but also that they recognize it suitability for pain management without the requirement of advanced skills or experienced users. Furthermore, the system enabled the definition and management of patient-oriented treatments with reduced therapist time. The study also revealed that the guidance of HCP at the beginning of the monitoring is crucial to patients' satisfaction and experience stemming from the usage of the system as evidenced by the high correlation between the recommendation of the application, and it suitability to improve pain management and to provide medical information. There were no significant differences regarding to improvements in the quality of pain treatment between intervention group and control group. Based on the data collected during the RCT a clinical decision support system (CDSS) was developed so as to offer capabilities of tailored alarms, reports, and clinical guidance. This CDSS, called Patient Oriented Method of Pain Evaluation System (POMPES), is based on the combination of several statistical models (one-way ANOVA, Kruskal-Wallis and Tukey-Kramer) with an imputation model based on linear regression. This system resulted in fully accuracy related to decisions suggested by the system compared with the medical diagnosis, and therefore, revealed it suitability to manage the pain. At last, based on the aerospace systems capability to deal with different complex data sources with varied complexities and accuracies, an innovative model was proposed. This model is characterized by a qualitative analysis stemming from the data fusion method combined with a quantitative model based on the comparison of the standard deviation together with the values of mathematical expectations. This model aimed to compare the effects of technological and pen-and-paper systems when applied to different dimension of pain, such as: pain intensity, anxiety, catastrophizing, depression, disability and interference. It was observed that pen-and-paper and technology produced equivalent effects in anxiety, depression, interference and pain intensity. On the contrary, technology evidenced favourable effects in terms of catastrophizing and disability. The proposed method revealed to be suitable, intelligible, easy to implement and low time and resources consuming. Further work is needed to evaluate the proposed system to follow up participants for longer periods of time which includes a complementary RCT encompassing patients with chronic pain symptoms. Finally, additional studies should be addressed to determine the economic effects not only to patients but also to the healthcare system

충수염 의증 청소년 및 젊은 성인에서 2-mSv CT와 기존 선량 CT의 민감도 및 특이도: LOCAT의 사후 하위그룹 분석

학위논문(박사)--서울대학교 대학원 :융합과학기술대학원 융합과학부,2019. 8. 이경호.Introduction: To explore heterogeneity across patient or hospital characteristics in the diagnostic sensitivity and specificity of 2-mSv CT relative to conventional-dose CT (CDCT) in adolescents and young adults with suspected appendicitis. Methods: We used the per-protocol analysis set of a large randomized controlled noninferiority trial conducted between Dec 2013, and Aug 2016, comparing 2-mSv CT and CDCT (typically 7 mSv). The data included 2,773 patients (median age [interquartile range], 28 [21–35] years) and 160 radiologists from 20 hospitals. We tested for heterogeneity in sensitivity and specificity for the diagnosis of appendicitis across predefined subgroups by patient sex, body size, clinical risk scores for appendicitis, time of CT examination (i.e., working hours [typically 08:00–17:00 of working days] vs. after hours), CT machines, radiologists experience, previous site experience in 2-mSv CT, and site practice volume. We drew forest plots and tested for additive or multiplicative treatment-by-subgroup interaction on sensitivity and specificity. Results: The 95% CIs for the between-group differences, particularly for sensitivity, were wide due to small sizes (< 200) for the subgroups of extreme body sizes, high clinical risk score for appendicitis, newer CT machines, hospital with prior experience in 2-mSv CT, and hospitals with small appendectomy volume. Otherwise, the 95% CIs in most subgroups contained the previously reported overall between-group differences as well as null hypothesis value (i.e., 0). There was no significant additive or multiplicative interaction for either sensitivity or specificity. Conclusions: We found no notable subgroup heterogeneity, which implies that 2-mSv CT can replace CDCT in diverse populations. Further studies are needed for the populations for which our subgroups were small.서론: 본 연구는 충수염 의증 청소년 및 젊은 성인에서 기존 CT와 비교하여 2-mSv CT의 진단 민감도 및 특이도에서 환자 또는 병원의 특성에 따른 이질성이 있는지를 탐색하는 연구임. 방법: 본 연구는 2013년 12월에서 2016년 8월 사이에 15–44세의 환자에서 2-mSv CT와 기존 선량 CT (일반적으로 7 mSv)를 비교한 대규모 비열등성 무작위배정 임상시험의 프로토콜 별 분석세트를 사용함. 본 연구에는 20개 병원에서 2,773명의 환자 (중앙값 연령 [사분위수 범위], 28 [21–35]세)가 포함되었으며, 160명의 판독의가 참여함. 환자의 성별, 신체 크기, 충수염에 대한 임상 위험 점수, CT 검사시간 (일과시간 [근무일 기준 오전 8시부터 오후5시] 또는 일과시간 이후), CT 장비, 판독의의 경험정도, 2-mSv CT에 대한 이전 경험 여부, 그리고 병원의 임상규모 등의 사전 정의된 하위 그룹에서 충수염 진단을 위한 민감도 및 특이도의 이질성을 테스트함. 두 군의 차이를 숲그림으로 제시하고, 민감도와 특이도에 대한 덧셈 및 곱셈 상호작용을 테스트함. 결과: 많이 날씬하거나 뚱뚱한 경우, 충수염 염증 반응 점수가 높은 경우, 최신 CT 기기를 사용한 경우, 2-mSV CT 의 이전 경험이 있는 병원, 그리고 충수절제술 규모가 작은 병원의 경우 등 특정 하위 그룹은 작은 크기 (< 200)로 인해 민감도에 대한 95 % 신뢰구간이 넓었음. 그 외, 대부분의 하위 그룹에서 그룹 간 차이에 대한 95 % 신뢰구간은 이전 보고된 전체 그룹 간 차이 및 귀무 가설 값 (즉, 0)을 포함하였음. 2-mSv CT 군과 기존 선량 CT 군 간에 민감도 및 특이도에서 덧셈 또는 곱셈 상호작용을 보이는 하위 그룹은 없었음. 결론: 충수염 의증 청소년과 젊은 성인에서 2-mSv CT와 기존 선량 CT 간에 민감도와 특이도에서 이질성을 보이는 하위그룹은 없었음. 이는 2-mSv CT가 다양한 집단에서 기존 선량 CT를 대체할 수 있음을 의미함. 다만, 본 연구에서 작은 크기를 가진 일부 하위 그룹에 대해서는 추가적인 연구가 필요함.INTRODUCTION 1 Motivations of LOCAT 1 Purposes of LOCAT 3 Motivations of Dissertation Research 4 Purposes of Dissertation Research 5 BACKGROUND 7 Epidemiology of Appendicitis and CT utilization 7 Imaging Utilization 7 Popularity of CT 8 CT Radiation 9 Radiation Dose Level 10 Typical Radiation Dose for Multi-purpose Abdomen CT 10 Typical Radiation Dose for Appendiceal CT 11 Low Doses Explored in Research Settings 12 Carcinogenic Risk Associated with CT Radiation 12 Controversy 13 ALARA Principle 14 Efficacy and Effectiveness of LDCT Compared to CDCT 15 Clinical Outcome 19 Diagnostic Performance 20 Inter-observer Agreement 21 Differentiation between Complicated vs. Uncomplicated Appendicitis 22 Image Quality 24 Visualization of the Appendix 24 Alternative Diagnoses 25 Step-wise Multimodal Diagnostic Approach Incorporating LDCT 27 Patient Subgroups Less Benefited from LDCT 27 Selective Utilization of LDCT 29 Additional Imaging Test(s) Following LDCT 30 Imaging Techniques for LDCT for Suspected Appendicitis 31 Intravenous Contrast Enhancement 31 Contrast-enhancement Phase 31 Enteric Contrast 32 Anatomical Coverage 32 Tube Current 33 Tube Potential 34 Iterative Reconstruction 34 Image Reconstruction Thickness 35 Coronal Reformation 35 Sliding-Slab Averaging Technique 36 Image Interpretation and Reporting for LDCT 37 Diagnostic Criteria for Appendicitis 37 Structured Reporting 38 Other Practical Issues in Implementing LDCT 39 Dedicated Protocol for Appendiceal CT 40 Education for Referring Physicians and Surgeons 41 Education for Radiologists 42 Dose Calibration and Monitoring 43 MATERIALS AND METHODS 47 Study Overview 47 Practice Setting 48 Pre-registration Procedures 48 Study Organization and Site Recruitment 49 Site Activation 50 Patients 51 Eligibility Criteria 54 Clinical Suspicion for Appendicitis 55 The Need for CT Examination 55 Generalizability 56 Representativeness of Study Sample 57 Withdrawal Criteria 58 Randomization 58 Index Test 59 CT Image Acquisition and Archiving 66 Radiation Doses 69 Record of Modulated Radiation Dose 71 Target Median DLP Values for the 2-mSv CT and CDCT groups 71 Calibration of Radiation Doses 72 Estimation of Carcinogenic Risk Associated with CT Examination 74 Image Interpretation 75 Radiologists and CT Reports 76 Radiologist Training 78 Considerations Regarding Technical Advantages over Previous Studies 79 Image Submission 80 Co-intervention 81 Additional Imaging 82 General Treatment Guidelines 82 Follow-up 84 Endpoints in LOCAT 85 Primary Endpoint 86 Secondary Endpoints 86 Considerations for NAR and APR 89 Changes in Endpoints 89 Reference Standards 91 Overview of Reference Standards 91 Definition of Acute Appendicitis 92 Mild or Early Acute Appendicitis 92 Appendiceal Diverticulitis 93 Cases of Delayed Appendectomy 93 Periappendicitis 93 Definition of Appendiceal Perforation 94 Reporting AEs 95 Definition of AE 96 Definition of SAE 97 AE Characteristics 97 Grade 98 Expected/Unexpected AEs 98 Attribution 98 Individual Symptoms vs. Single Diagnosis 99 Who Should Report AEs 99 How to Report AEs 99 Follow-up for AEs 100 Ethical Considerations 100 Ethics and Responsibility 100 Informed Consent Form 101 Data Security and Participant Confidentiality 101 Early Stopping Rules in LOCAT 101 Data Management 102 Case Report Forms 103 Monitoring Participant Accrual 103 Monitoring Data Quality 103 Data and Safety Monitoring Board 105 Statistical Analysis 105 Considerations for Primary Endpoint 105 Analysis Plans 107 Sample Size 108 Sample Size Considerations 108 Final Sample Size 110 Rationale for the Noninferiority Margin 111 Reported NARs Following Preoperative CT 111 Reported NARs in Patients Without Preoperative CT 112 Sample Size Considerations on APR 113 Subgroup Analyses for APR and NAR 114 Subgroup Analyses for Diagnostic Performance 116 RESULTS 119 Patient Characteristics 119 Overall Diagnostic Performance 123 Subgroups of Limited Comparison 123 Between-group Differences for Subgroups 123 Heterogeneity 131 DISCUSSION 132 CONCLUSION 139 REFERENCES 140 APPENDIX 164 Abstract in Korean 176Docto

Advances in the diagnosis of acute aortic syndromes: Role of imaging techniques.

Aortic diseases include a wide range of pathological conditions: aortic aneurysms, pseudoaneurysms, acute aortic syndromes, atherosclerotic and inflammatory conditions, genetic diseases and congenital anomalies. Acute aortic syndromes have acute onset and may be life-threatening. They include aortic dissection, intramural haematoma, penetrating aortic ulcer and traumatic aortic injury. Pain is the common denominator to all acute aortic syndromes. Pain occurs regardless of age, gender and other associated clinical conditions. In this review, we deal with the main findings in the clinical setting and the most recent indications for diagnostic imaging, which are aimed to start an appropriate treatment and improve the short- and long-term prognosis of these patients. © The Author(s) 2016

Evolution and challenges in the design of computational systems for triage assistance

AbstractCompared with expert systems for specific disease diagnosis, knowledge-based systems to assist decision making in triage usually try to cover a much wider domain but can use a smaller set of variables due to time restrictions, many of them subjective so that accurate models are difficult to build. In this paper, we first study criteria that most affect the performance of systems for triage assistance. Such criteria include whether principled approaches from machine learning can be used to increase accuracy and robustness and to represent uncertainty, whether data and model integration can be performed or whether temporal evolution can be modeled to implement retriage or represent medication responses. Following the most important criteria, we explore current systems and identify some missing features that, if added, may yield to more accurate triage systems

CT dose optimization with model based iterative reconstruction

The aim of this thesis is to assess the feasibility of using model-based iterative reconstruction (MBIR) to develop new low-dose CT (computed tomography) protocols in the areas of neck, chest, and abdominal imaging without compromising diagnostic performance. Medical imaging has become the largest source of radiation exposure for humans other than natural background radiation. The availability of and improvements in diagnostic imaging have led to a sevenfold increase in the use of imaging over the past 30 years. This is especially true for CT, with a 7.8% annual increase in the use of CT from 1996 to 2010. The major concern associated with the widespread uptake of CT is the parallel increase in radiation exposure incurred by patients, and while the relationship of diagnostic radiation exposure to a quantifiable risk of cancer induction remains a controversial topic, physicians are beholden to keep radiation doses from diagnostic imaging as low as reasonably possible to limit the risk of radiation-induced cancer. We conducted preliminary phantom and cadaveric studies to examine the performance of MBIR at different radiation dose levels in the thorax and abdomen. Cadavers and phantoms provide a means of safely assessing new technologies and optimizing scan protocols prior to clinical validation. An anthropomorphic torso phantom and 5 human cadavers were scanned at varying radiation dose levels and images reconstructed using three different reconstruction techniques: filtered back projection, hybrid IR and MBIR. MBIR reduced image noise and improved image quality even in CT images acquired with a mean radiation dose reduction of 62%, compared with conventional dose studies reconstructed with hybrid IR, with lower levels of objective image noise, superior diagnostic acceptability and contrast resolution, and comparable subjective image noise and streak artifact scores. We subsequently performed clinical studies with the objectives of assessing MBIR as a tool for image quality improvement and radiation dose reduction in CT, and for the development of new low-dose carotid angiography, chest, and abdominopelvic CT protocols. We developed a low-dose carotid CTA protocol reconstructed with MBIR comparable to a conventional dose CTA protocol in terms of image quality and diagnostic accuracy while enabling a dose reduction of 49.6%. 20 patients were scanned using a split-dose technique with radiation dose divided into a low-dose acquisition reconstructed with MBIR and a conventional dose acquisition reconstructed with hybrid IR. Mean effective dose was significantly lower for the low-dose studies (1.84mSv versus 3.71mSv) and subjective image noise, contrast resolution, and spatial resolution were significantly higher for the low-dose studies. There was excellent agreement for stenosis grading accuracy between low- and conventional dose studies (Cohen κ = 0.806). A modified low-dose CT thorax protocol reconstructed with MBIR was also developed to monitor pulmonary disease progression in patients with cystic fibrosis with our low-dose protocol enabling the acquisition of a full-volume diagnostic quality chest CT at a dose equivalent to that of a chest radiograph (0.09±0.01mSv). Finally, we assessed the feasibility of low-dose abdominopelvic CT performed with MBIR as a radiation dose reduction strategy for imaging patients presenting with acute abdominal pain. A 74.7% mean radiation dose reduction was achieved with scans performed in the peri- and submillisievert range in patients of normal and low BMI, respectively, without compromising diagnostic performance. Dose reduction to the submillisievert range for patients with an elevated BMI was a challenge. The current era is extremely exciting in terms of radiation dose optimization in CT. This thesis is a demonstration of the potential for substantial reductions in radiation exposure, when the benefits of iterative reconstruction are combined with automated tube current modulation and other CT scanner technologies. The combination of all these hardware and software developments is now seeing major benefits for the patient and moving beyond the narrow aim of radiation exposure reduction to a complete change in practice, towards replacement of conventional radiography with low-dose CT, without any penalty for the patient in terms of radiation exposure