Acute upper gastrointestinal bleeding: using quality data for operational and clinical improvement

ISABEL MARIA TEIXEIRA DE CARVALHO PEDROTO TESE DE DOUTORAMENTO APRESENTADA AO INSTITUTO DE CIÊNCIAS BIOMÉDICAS ABEL SALAZAR DA UNIVERSIDADE DO PORTO EM CIÊNCIAS MÉDICAS 2014 ACUTE UPPER GASTROINTESTINAL BLEEDING: USING QUALITY DATA FOR OPERATIONAL AND CLINICAL IMPROVEMENT Legislação e regulamentos aplicáveis ao Doutoramento em Ciências Médicas: Decreto-Lei nº 74/2006, de 24 de março, com a redação dada pelos Decretos-Lei nº107/2008 e 230/2009, de 25 de junho e 14 de setembro. Regulamento geral dos terceiros ciclos de estudos da Universidade do Porto, aprovado pelo despacho reitoral GR.05/11/2009, de 24 de novembro. Deliberação n.º 3218/2009 de 24 de novembro do Reitor da Universidade do Porto, publicada em Diário da República, 2.ª série, n.º 232 de 30 de novembro. Regulamento Específico do Doutoramento em Ciências Médicas aprovado da Comissão Coordenadora do Conselho Científico do Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, a 21 de abril de 2010. A capa da tese obedece ao manual de imagem da Reitoria da Universidade do Porto. ISABEL MARIA TEIXEIRA DE CARVALHO PEDROTO ACUTE UPPER GASTROINTESTINAL BLEEDING: USING QUALITY DATA FOR OPERATIONAL AND CLINICAL IMPROVEMENT Tese de Candidatura ao grau de Doutor em Ciências Médicas submetida ao Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto. Orientador: Doutor Jorge Alberto Areias Categoria – Professor Catedrático Aposentado Afiliação – Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto. Coorientadores: Doutora Suzete Gonçalves Categoria – Investigadora Afiliação – Centro de Estudos e Investigação em Saúde na Universidade de Coimbra Doutor Mário Dinis Ribeiro Categoria – Professor Catedrático Convidado Afiliação – Faculdade de Medicina da Universidade do Porto / Preface 8 I wrote this thesis to fill what I perceived as a critical gap in healthcare services; to understand the value of data and use them in the whole process of care, as the basis for delivering quality care and try to overcome the economic constraints. It has been an outstanding and extremely rewarding journey. / Acknowledgments 9 ACKNOWLEDGMENTS Em janeiro de 1989 cheguei pela primeira vez ao Hospital de Santo António onde encontrei o saudoso Dr. Soares de Sousa, com quem tive o privilégio de trabalhar no serviço de medicina. Os seus ensinamentos, as suas palavras de estímulo, a sua amizade, fizeram com que sentisse o Hospital de Santo António como aquele que viria a tornar-se a minha casa de sempre. Um ano depois integrei o serviço de Gastrenterologia então dirigido pelo Dr. Amílcar Mascarenhas Saraiva, clínico por quem nutro profunda admiração pela forma como sempre me tratou, pelo rigor que era seu apanágio e pela amizade que desde então perdura. Teve um papel muito importante nos primeiros anos da minha formação e por isso lhe devo um enorme tributo de gratidão e apreço. Foi meu orientador de internato o Professor Doutor Jorge Areias, a quem dirijo as minhas primeiras e sentidas palavras de agradecimento. Sempre me incentivou e estimulou para iniciar o doutoramento. Espero com esta tese poder expressar-lhe a dimensão e profundidade do meu reconhecimento e amizade. Ao Dr.Carlos Pinho pelo exemplo de persistência, determinação e coragem. Ao Dr. Sollari Allegro, atual Presidente do Conselho de Administração e meu colega gastroenterologista, devo também um especial tributo. Devo-lhe muito do que aprendi no âmbito da Gastrenterologia, em particular no domínio das técnicas e no manuseamento da hemorragia digestiva. Foi o Dr. Sollari Allegro que me convidou para assumir as funções de gestora de risco clinico e, mais tarde, para dirigir o departamento de qualidade. As tarefas de que fui incumbida despertaram em mim o gosto e interesse pela gestão do risco clínico e pela importância da qualidade, atributos essenciais da gestão hospitalar de excelência. Pela amizade com que me distinguiu ao longo destes anos e que sempre procurei retribuir, o meu profundo agradecimento ao Dr. Sollari Allegro que é também para mim e para todos os que o conhecem um edificante exemplo de coragem, força e inesgotável pertinácia. Uma palavra de fraternal amizade a todos os meus colaboradores no departamento de qualidade que dirigi durante 3 anos. / Acknowledgments 10 Foi um trabalho árduo, estimulante, desafiante, em que foi preciso vencer inúmeros obstáculos, mas sempre pautado por um forte espírito de equipa, por um acrisolado sentido de missão e por um entusiasmo contagiante ao serviço da mudança e de uma cultura organizativa moderna, eficiente e humanista. Cabe aqui também um agradecimento muito especial dirigido ao Prof. Doutor Martins da Silva, cujo convite para ser sua adjunta na direção clínica me fez crescer e entender ainda mais a necessidade de uma governação clínica na qual os médicos devem liderar o processo e assumirem-se como os principais protagonistas da mudança. Estou igualmente grata à Professora Doutora Suzete Gonçalves, minha coorientadora, e de quem recebi preciosos ensinamentos enquanto discente das suas aulas de economia da saúde no âmbito da pós-graduação em gestão para médicos, o que muito contribuiu para a minha formação e para expandir os horizontes do meu conhecimento. Ao Professor Doutor Mário Dinis-Ribeiro pelo estímulo constante e pela forma como tem sabido prestigiar a gastroenterologia portuguesa em Portugal e na Europa. A todos os elementos do meu Serviço, médicos, enfermeiros, assistentes técnicos e operacionais, pela colaboração no desempenho deste trabalho e pelas provas de solidariedade e amizade de que deram mostras ao longo destes anos. A todos os colegas que integram a urgência regional de Gastrenterologia, pela participação ativa na recolha de dados e desempenho ímpar neste modelo organizativo. A todos os elementos do serviço de urgência e das unidades intermédia e de cuidados intensivos, da área médica e cirúrgica, que tão eficazmente lidam com estes doentes e colaboram com o serviço de gastrenterologia. Uma palavra muito especial de agradecimento ao Conselho de Administração do Centro Hospitalar do Porto pela compreensão dos objetivos do trabalho, pela disponibilidade e palavras de encorajamento permanente, o que em muito concorreu para a sua realização. Ao Professor Doutor Cardoso de Oliveira, o meu reconhecimento por todos os ensinamentos, pelos desafios para integrar novos projetos na área da qualidade clínica, como a Associação para a Segurança dos Doentes, mas sobretudo, pela compreensão e pela forma carinhosa como sempre me tratou. A todos os meus amigos, uma palavra especial de agradecimento pela paciência e amizade. / Acknowledgments 11 A toda a minha família, a expressão do meu amor. / List of Published or Accepted for Publication Papers 13 LIST OF PUBLISHED OR ACCEPTED FOR PUBLICATION PAPERS All papers are referred to in the text by the corresponding Roman numeral. The papers are presented in the chronological order of their production: Order Description Order Description Paper I Pedroto I, Dinis-Ribeiro M , Ponchon T. Is timely endoscopy the answer for cost-effective management in acute upper gastrointestinal bleeding? Published in Endoscopy 2012; 44(08): 721-722 Paper II Pedroto I, Amaro P, Romãozinho JM. Health systems organization for emergency care. Published in Best Practice & Research Clinical Gastroenterology 27 (2013) 819–827 Paper III Pedroto I, Maia L, Salgueiro P, Teles de Sampaio E, Küttner Magalhães R, Magalhães MJ, Pinto R, Dias C, Dinis-Ribeiro M. Out-ofHours Endoscopy for Non-Variceal Upper Gastrointestinal Bleeding Accepted for publication in Scandinavian Journal of Gastroenterology Manuscript ID SGAS-2014-0531.R1: proofs revised. / List of Abbreviations 15 LIST OF ABBREVIATIONS AUGIB Acute upper gastrointestinal bleeding CBA Cost-benefit analysis CEA Cost-effectiveness analysis CHP Centro Hospitalar do Porto CIs Clinical Indicators CUA Cost-utility analysis ED Emergency department ED-CHP Emergency department of Centro Hospitalar do Porto EGD Upper endoscopy ENERGIB European Study of Nonvariceal upper gastrointestinal bleeding GBS Glasgow Blatchford Score GRS Global Rating Scale IOM Institute of Medicine NHS Britain's National Health Service NVAUGIB Non-variceal acute upper gastrointestinal bleeding PDCA Plan, Do, Check, Act cycle PUB Peptic ulcer bleeding QALYs Quality-adjusted-life-years QI Quality Improvement URGE Regional Gastroenterology Emergency WHO World Health Organization / List of Figures and Tables 17 LIST OF FIGURES Figure 1 Out-of-hours endoscopy is under crisis: an Ishikawa diagram clarifies the potential root causes of the problem 30 Figure 2 The quality dimensions proposed by the Institute of Medicine 58 Figure 3 The Deming cycle: Plan, Do, Check, Act, a systematic approach to problem solving 65 Figure 4 Factors determining the outcome of care in health care delivery 81 Figure 5 The North of Portugal and URGE localization 111 Figure 6 Emergency check sheet 119 Figure 7 Patient enrollment between January 2010-December 2012 133 Figure 8 Pareto diagram: referrers hospitals versus the number of patients 134 Figure 9 Geographic visualization: flow of patients and hospital's contribution 135 Figure 10 Planning after EGD 143 Figure 11 Patient workflow described as a multi-step process: visualizing the patient's journey 147 Figure 12 Before and After the Model‘s implementation and assessment 182 LIST OF TABLES Table 1 The gurus and their approach to quality improvement 64 Table 2 The seven basic tools of quality 66 Table 3 Definitions of clinical indicators 72 Table 4 Example of clinical indicator's concept 73 Table 5 Risk Stratification Scoring Systems 103 Table 6 The evaluation framework used: how was the service used 117 Table 7 The evaluation framework used: how was the service provided 118 Table 8 Baseline characteristics of patients and data recorded 124 Table 9 Overall results: age groups vs. admission status 134 Table 10 Overall results: the demand according to the year and month of the year vs. time and admission status 136 Table 11 Overall results: the demand according to weekday and weekend vs. time and admission status 138 Table 12 Overall results - Patient flow: Lead time 139 Table 13 Overall results: Patients characteristics for NVAUGIB and in subgroups according to time and admission status 140 Table 14 Overall results: Patients outcomes for NVAUGIB and in sub-groups according to time and admission status 144 Table 15 Our Process Clinical Indicators 180 / Table of Contents 24 CHAPTER III ................................................................................................................. 107 RESEARCH METHODOLOGY ...................................................................................... 107 IIIa. Setting ................................................................................................................................. 109 IIIb. The Process ......................................................................................................................... 113 IIIc. Patients and Data Analysis .................................................................................................. 121 IIId. Statistical Analysis ............................................................................................................... 125 CHAPTER IV ................................................................................................................. 129 RESULTS ...................................................................................................................... 129 IVa. Overall Results ..................................................................................................................... 131 IVb. Main Results ........................................................................................................................ 145 CHAPTER V .................................................................................................................. 171 DISCUSSION ................................................................................................................ 171 CHAPTER VI ................................................................................................................. 185 CONCLUSIONS ............................................................................................................ 185 VIa. Concluding Remarks ............................................................................................................ 187 VIb. Practical Implications .......................................................................................................... 191 VIc. Further Research ................................................................................................................. 195 APPENDIX .................................................................................................................... 199 REFERENCES .............................................................................................................. 225 CHAPTER I INTRODUCTION Ia. Context Ib. Outline and Aims of the Thesis IIc. Thesis Structure CHAPTER I INTRODUCTION Ia. Context Ib. Outline and Aims of the Thesis IIc. Thesis Structure / Chapter I - Introduction 29 I. INTRODUCTION Ia. Context Why is this research important? Improving the quality of services is now a key requirement within any health institution. It is about making healthcare safer, effective, patient centered, timely, efficient and equitable. In the past decade, there has been a great focus on improving the quality of health services, but the boards are being challenged to respond to the rigor imposed by economic constraints. Furthermore, acute upper gastrointestinal bleeding (AUGIB) is one of the most common emergency medical admissions for gastroenterology and has a significant inpatient mortality of 10% that has not improved over the last two decades (van Leerdam, Vreeburg et al. 2003; Targownik and Nabalamba 2006; Lanas, Garcia-Rodriguez et al. 2009). With our ageing population, comes a number of health challenges in this area (Yachimski and Friedman 2008). Although the overall incidence of AUGIB seems to have declined since the 1990s, the studies suggest that people aged more than 60 years constitute an increasing proportion of those presenting with AUGIB (Thomopoulos, Vagenas et al. 2004; Targownik and Nabalamba 2006; Lanas, Garcia-Rodriguez et al. 2009). Also, advanced age has been consistently identified as a risk factor for mortality in patients with AUGIB, in whom the outcome is influenced also by the presence of medical comorbidities, increased prescriptions for these comorbidities and interactions between the two (Cappell and Nadler 1995; Rockall, Logan et al. 1995; Hasselgren, Blomqvist et al. 1998; Hasselgren, Carlsson et al. 1998; Yamaguchi, Yamato et al. 2003; Baradarian, Ramdhaney et al. 2004; Thomopoulos, Vagenas et al. 2004). This calls for a timeliness and coordinated approach from diagnosis to treatment, in order to optimize favorable outcomes. Endoscopy in AUGIB is a time-critical procedure that should be performed in the first 24h (Barkun 2010). The implementation of early discharge policies is an important issue in today´s health care, but, in these cases, necessitates a rapid diagnostic endoscopic service. So, if this procedure is performed early, may avoid expensive and unnecessary / Chapter I - Introduction 30 Out-of-hours endoscopy is under crisis Equipment Human resources Economic resources PatientsProcess Health policy High risk Comorbidities Scarce High impact Technical performance Lack of experience Lack of supervision Protocols Coordination Structures Transfer policy Cleaning and reprocessing Impact on routine work Figure 1: Out-of-hours endoscopy is under crisis This Ishikawa diagram intends to give a visualization of the potential causes of a problem called out-of-hours endoscopy. inpatient treatment with early discharge and reduction of the length of stay. However, how urgently endoscopy needs to be done is still debated (Pedroto, Dinis-Ribeiro et al. 2012). What is lacking in the current knowledge Some studies have identified serious gaps within the hospital like inadequate out-of hoursservice, inappropriate triage and staff shortages in the management of AUGIB (da Silveira, Lam et al. 2006; Hearnshaw, Logan et al. 2010; Jairath, Kahan et al. 2012). But outside factors affecting the hospital must also be taken into account: inadequate access of the general population to specialists; delayed ambulance service; the all structure of the delivery system (da Silveira, Lam et al. 2006). The diagram bellow clarifies the factors discriminated in the studies mentioned above, and draws attention for the need of a systemic approach (figure 1). So far as we know, there is no information available on the clinical management of AUGIB in relation to the current organization of the emergency health care services in Portugal, namely non-variceal acute upper gastrointestinal bleeding (NVAUGIB), neither a single cause and effect scenario to address timely endoscopy in northern Portugal. And, moreover, there is not a great deal of scientific analysis on these issues. / Chapter I - Introduction 31 Paper I and II assess this two issues, from the endoscopy perspective to the organizational level, which can be read at the end of this chapter. Context of the innovation AUGIB is a time-critical event, the care of which should be timely, patient-focused and consultant-based; a 24-hours-a-day, 7-days-a week, has the essential requirements for an emergency model of care and the service should be organized around the patient‘s needs. New models of care should be beneficial to patients and staff, rather than just being considered for purely economic or administrative reasons. But, unlike other clinical areas, cardiac or stroke care, the field of emergency care in gastrointestinal emergencies, currently lacks a uniform set of metrics which informs providers, administrators, and consumers about the status of their care. All of this calls for a coordinated approach and organizational (national, regional or local) models of care. These must become the driving force for organizing, evaluating, and facilitating medical care across the full care cycle. We found no studies directly addressing the causal relationship between all three variables of care: structure, processes and outcomes, although in some, associations between outcomes and resources could be inferred. Our review suggested that more research is needed to establish a robust and effective model of gastroenterology emergency service delivery (Pedroto, Amaro et al. 2013). In northern Portugal, none of the institutions had sufficient resources to ensure a 24-hour gastroenterology emergency service. In October 2006, an out-of-hours endoscopy regional center was set up (Regional Gastroenterology Emergency-URGE) in one tertiary trust in Oporto covering a population of three million. This is the place where 30 consultant gastroenterologists from eight hospitals and eight nurses from the endoscopy unit are integrated as the gastroenterology emergency team, everyday from 8pm to 8am; they are responsible for handling gastroenterology emergencies, especially those requiring urgent endoscopy. Although ppopulation-base epidemiology data are important to get insight in the actual healthcare problem, it is vital to understand the current demand, outcomes and causes of NVAUGIB to inform and improve future management of this organizational acute model of care in northern Portugal. In northern Portugal, the management of NVAUGIB in the past decade was dependent on the organizational structure of each hospital. Until October 2006, endoscopy was / Chapter I - Introduction 32 performed within normal working hours only, i.e. usually the next working day after admission. The establishment of a dedicated out-of-hours endoscopy unit gave us the opportunity and clinical material to inquire whether the new model of treatment covers the various dimensions of quality in health care. CHAPTER I INTRODUCTION Ia. Context Ib. Outline and Aims of the Thesis IIc. Thesis Structure / Chapter I - Introduction 41 / Chapter I - Introduction 42 / Chapter I - Introduction 43 / Chapter I - Introduction 44 / Chapter I - Introduction 45 / Chapter I - Introduction 46 / Chapter I - Introduction 47 / Chapter I - Introduction 48 / Chapter I - Introduction 49 / Chapter II - Background 57 II. BACKGROUND IIa. Quality in Health Care IIa1. Definition and Dimensions of Quality Over time, quality has been defined in several ways. Within healthcare, there is no universally accepted definition of quality. Quality of care encompasses many definitions, dependent on the author or institute defining the term, or if they are used in relation to health care or health care systems. For instance, the Portuguese National Health Service represents a universal care system run by the government's Department of Health in a structured and uniform manner. But, but for example, The United States' health care system, is operated by several different entities, including the government, managed care organizations, and insurance companies. Donabedian, the leading figure in the theory and management of quality of care, had already suggested that quality will always differ from person to person, largely dependent on ―where we are located in the system of care and on what the nature and extent of our responsibilities are‖ (Donabedian 1988). Every healthcare organization provides a different level of quality, with higher levels of quality always correlating with the experience of those providing the care (HS 1990). High quality standards do rely heavily on a well-organized system, with real improvement in quality dependent on continuous improvement throughout the organization, through constant effort to reduce waste, rework, and complexity (Berwick 1989). The more efficient and content the work environment is, the higher the quality of care experienced by the patient. At the present, I believe that for most of our health care professionals, the definitions of quality rely just on the technical excellence with which care is provided and the characteristics of interactions between provider and patient, as stated by Blumenthal (Blumenthal 1996). In 1980, Donabedian defined care of high quality as ―that kind of care which is expected to maximize and inclusive measure the patient welfare, after one has taken account of the balance of expected gains and losses that attend the process of care in all its parts" (Donabedian 1980). In 1984, the American Medical Association defined high-quality care as care ―which consistently contributes to the improvement or maintenance of quality and/or duration of life"(1986). The association identified specific attributes of care that / Chapter II - Background 58 Figure 2: The quality dimensions proposed by the Institute of Medicine should be examined in determining its quality, including an emphasis on health promotion and disease prevention, timeliness, the informed participation of patients, attention to the scientific basis of medicine, and the efficient use of resources. One of the most cited definitions, was formulated by the Institute of Medicine (IOM) in 1990, and defined quality as the ―degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge" (Lohr KN 1992). And in fact, the US health care system has been at the forefront of health care QI efforts for over a century. Dr. Ernest Amory Codman (1869– 1940), a physician at the Massachusetts General Hospital in Boston, was among the first in the developed world to highlight the problem of poor quality in health care. He subsequently set a standard for open, honest, and public evaluation of the end results of medical and hospital care (Neuhauser 1990). Since then, much work has been done in the USA by governmental agencies such as the Joint Commission on Accreditation of Healthcare Organizations and the Agency for Healthcare Quality and Research, and various professional societies. However, fourteen years ago, two reports from the IOM suggested that there was a long way to go before Americans could enjoy safe and clinically effective service (Institute of Medicine 1999; Medicine 2001). The first report, To Err is Human estimated that nearly 44,000 Americans died each year as a result of medical errors. More people died in a given year as a result of medical errors than from motor vehicle accidents, breast cancer, or AIDS. Total national costs of preventable adverse events were estimated to be between $ 17 billion and $29 billion. The second IOM report Crossing the Quality Chasm, asked for a fundamental change, recommending that the delivery of health care in the 21st century should be based on 6 key dimensions: 1) safety—avoid injury to patients from the care that is intended to help them; 2) timeliness—reduce waits and harmful delays; 3) effectiveness—provide services based on scientific knowledge to all who could benefit and refrain from providing services to those not likely to benefit [avoiding overuse and underuse, respectively]; 4) efficiency—avoid waste; 5) equitability—provide care that does not vary in quality because of personal characteristics such as gender, ethnicity, geographical location, and socioeconomic status; 6) patient centeredness—provide care that is respectful of and responsive to individual patient preferences, needs, and values. Other countries have faced similar challenges. The Britain's National Health Service (NHS), as constituted in 1948, was a / Chapter II - Background 59 universal system, funded predominantly by taxation, that made health care available to the whole population and had a strong focus on health care QI, especially since the early 1990s. At that time, emphasis was placed on improving standards of care, and all professionals were mandated to scrutinize their practices through clinical audit. Clinical audit required professionals to look systematically at the procedures used for diagnosis, care, and treatment; to examine how associated resources were being used; and to investigate the effect care had on the outcome and quality of life for the patient. Various national and regional initiatives were launched to support these efforts and many organizations involved. I think that one of the best definitions of quality belongs to Harteloh (Harteloh 2003): ―Quality is an optimal balance between possibilities realized and a framework of norms and values.‖ This conceptual definition reflects the fact that quality is an abstraction and does not exist as a discrete entity. Rather it is constructed based on an interaction among relevant actors who agree about standards (the norms and values) and components (the possibilities). This is in accordance with Davila's abstract definition "For many, quality health care is like beauty or pornography—they know it when they see it but they just can‘t define it" and " Ultimately, the answer to the question ―Should it be done?‖ rather than ―Can it be done?‖ will determine what quality health care is and is not" (Davila 2002; Davila 2002)). The Portuguese National Health Plan for 2012-2016 defines quality in health as "... the provision of affordable and equitable healthcare, with an excellent professional level, taking into account the available resources, while achieving the citizen's adhesion and satisfaction. It also implies the adequacy of healthcare to the needs and expectations of citizens and the best possible performance". In summary, there are many different definitions of quality in health care. The characteristics emphasized vary according to the perspectives of the people and the organizations offering them. What is common to all definitions is the need to see quality of care as much more than just a matter of technical skills and the supply of services. Good quality of care must also respect the perspectives and needs of the patient and meet standards in ways that are safe, effective, patient-centered, timely, efficient and equitable. Regardless of what definition of quality of health care is used, it must be kept in mind that every system, every process and every patient are different. Those who work in health care need to find ways to make QI an integral component of everyone‘s work. This means / Chapter II - Background 60 investments in people, technology, and processes. Most importantly, it means the support of our leaders and their commitment. In spite of this difficulty in defining the concept, there has always been the need to measure and improve quality in health care. CHAPTER II BACKGROUND IIa. Quality in Health Care IIa1. Definition and Dimensions of Quality IIa2. Quality Assessment and Improvement IIa2.1. The History of Quality Improvement IIa2.2. Assessing and Measuring Quality in Healthcare IIb. Non-Variceal Acute Upper Gastrointestinal Bleeding IIb1. Occurrence and Mortality Trends IIb2. Interventions That Work IIb3. Interventions That Need More Study: controversies and areas of uncertainty / Chapter II - Background 63 II. BACKGROUND IIa2. Quality Assessment and Improvement IIa2.1. The History of Quality Improvement There is no single definition of QI, and no approach appears to be more successful than another. However, there are a number of definitions that describe QI as a systematic approach that uses specific techniques to improve quality. The most important ingredient in successful and sustained improvement is the way in which the change is introduced and implemented. The key elements are the combination of a change (improvement) with a method (an approach or specific tools) to achieve a better outcome. Understanding the basics of quality is important to our ability to improve it. Thus, this section briefly examines the main concerns that led to the pursuit of quality in industry. During the early days of manufacturing, an operative‘s work was inspected and a decision made whether to accept or reject it. As businesses became larger, so did this role, and full time inspection jobs were created. Later on, these changes led to the birth of the separate inspection department with a ―chief inspector‖, reporting to either the person in charge of manufacturing or the works manager. With the creation of this new department, there came new services and issues, standards, training, recording of data and the accuracy of measuring equipment; the need to address defect prevention emerged. Hence the quality control department evolved, in charge of which was a ―quality control manager‖, with responsibility for the inspection services and quality control engineering. The beginning of the 20th century marked the inclusion of ―processes‖ in quality practices. A ―process‖ is defined as a group of activities that takes an input, adds value to it and provides an output, such as when a chef transforms a pile of ingredients into a meal. Walter Shewhart, a statistician, began to focus on controlling processes in the mid–1920s, making quality relevant not only for the finished product but for the processes that created it. Shewhart recognized that industrial processes yield data and that this data could be analyzed using statistical techniques to see whether a process is stable and in control, or if it is being affected by special causes that should be fixed. They differ from product orientation in that they make quality relevant, not only for the finished product, but also, for the process that created it. At that time, Japan‘s industrial system was virtually destroyed, / Chapter II - Background 64 and it had a reputation for cheap imitation products. The Japanese recognized these problems and set about solving them with the help of some notable quality gurus like, Juran, Deming and Feigenbaum. In the early 1950‘s, quality management practices developed rapidly in Japan, and become a major theme in Japanese management philosophy, such that, by 1960, quality control and management had become a national issue. By the late 1960‘s/early 1970‘s Japan‘s imports into the USA and Europe increased significantly, due to its cheaper, higher quality products, compared to the Western counterparts. In 1969 the first international conference on quality control, sponsored by Japan, America and Europe, was held in Tokyo. In a paper given by Feigenbaum, the term ―total quality‖ was used for the first time, and referred to wider issues such as planning, organization and management responsibility. Ishikawa gave a paper explaining how ―total quality control‖ in Japan was different, it meaning ―company wide quality control‖, and describing how all employees, from top management to the workers, must study and participate in quality control. The quality revolution in the West was slow to follow, and did not begin until the early 1980‘s, when companies introduced their own quality programs and initiatives to counter the Japanese success (UK Governement 2005; ASQ 2011). A guru, by definition, is a good person, a wise person and a teacher. A quality guru should be all of these, plus have a concept and approach to quality within business that has made a major and lasting impact. Some examples of quality gurus are (table 1): Table 1: The gurus and their approach to quality improvement. Leader Approach W Edwards Deming Plan, Do, Check, Act (PDCA) cycle Joseph M Juran Quality Trilogy Armand V Feigenbaum Total Quality Control Kaoru Ishikawa Seven basic Tools of Quality Techniques such as his cause and effect "fishbone" tool. W Edwards Deming placed great importance and responsibility on management, at both the individual and company level, believing management to be responsible for 94% of quality problems. He introduced a new complete philosophy of management, statistical evidence that quality is built and the responsibility is to change from numbers to quality. / Chapter II - Background 65 Deming also encouraged a systematic approach to problem solving and promoted the widely known Plan, Do, Check, Act (PDCA) cycle (figure 3). The PDCA cycle is also known as the Deming cycle, although it was developed by a colleague of Deming, Dr Shewhart. The cycle is about learning and ongoing improvement, learning what works and what does not in a systematic way; and the cycle repeats; after one cycle is complete, another is started. Joseph M Juran developed the quality trilogy – quality planning, quality control and QI. Good quality management requires quality actions to be planned out, improved and controlled. Juran emphasized the necessity for ongoing QI through a succession of small improvement projects carried out throughout the organization. His ten steps to QI are: build awareness of the need and opportunity for improvement; set goals for improvement; organize to reach the goals; provide training; carry out projects to solve problems; report progress; give recognition; communicate results; keep score of improvements achieved and maintain. Each person along the chain, from product designer to final user, is a supplier and a customer. In addition, the person will be a process, carrying out some transformation or activity. Armand V Feigenbaum was the originator of ―total quality control‖, often referred to as total quality and defined as ―an effective system for integrating quality development, quality maintenance and QI efforts of the various groups within an organization, so as to enable production and service at the most economical levels that allow full customer satisfaction‖. He proposed three steps to quality: quality leadership; modern quality technology and organizational commitment. Kaoru Ishikawa made many contributions to quality, the most noteworthy being his emphasis on the human side of quality, the Ishikawa diagram and the assembly and use of the ―seven basic tools of quality‖, as detailed in table 2: Figure 3: The Deming cycle: Plan, Do, Check, Act, a systematic approach to problem solving. Adapted from the Department of Trade and Industry / Chapter II - Background 72 to patients as a consequence of how well professionals and organizational systems work. Indicators are, however, not a direct measure of quality (Mainz 2003). Table 3: Definitions of clinical indicators Mainz‘s definition (Mainz 2003) The United Kingdom‘s National Health Service definition (Collopy 2000) Australian Council on Healthcare Standards' definition (Rockville 2009) ―... the measure the extent to which set targets are achieved. They are expressed as numbers, rates, or averages that can provide a basis for clinicians, organizations, and planners aiming to achieve improvement in care and the processes by which patient care is provided. They can be measures of structure, process, and outcome, either as generic measures relevant for all diseases, or disease-specific measures that describe the quality of patient care related to a specific diagnosis.‖ ―… succinct measures that aim to describe as much about a system as possible in as few points as possible. Indicators help us understand a system, compare it and improve it.‖ 18 At a similar level, clinical indicators have been described as ―… a measure of the clinical management and/or outcome of care‖. ―... simply a measure of the clinical management and/or outcome of care. A well-designed indicator should ‗screen‘, ‗flag‘ or ‗draw attention‘ to a specific clinical issue. Usually rate based, indicators identify the rate of occurrence of an event. Indicators do not provide definitive answers; rather they are designed to indicate potential problems that might need addressing, usually demonstrated by statistical outliers or variations within data results. They are used to assess, compare and determine the potential to improve care. Indicators are therefore, tools to assist in assessing whether or not a standard in patient care is being met.‖ Indicators should be based on the best available evidence. Sackett et al. describe this as ‗the integration of best research evidence with clinical expertise and patient values‘. The strength of evidence for an indicator will determine its scientific soundness or the likelihood that improvement in the indicator will produce consistent and credible improvements in the quality of care (Sackett DL 2000). Namely, CIs measure the extent to which set targets are achieved. They are expressed as numbers, rates, or averages that / Chapter II - Background 73 can provide a basis for clinicians, organizations, and planners aiming to achieve improvement in care and the processes by which patient care is provided. An initial step towards good measurement practice begins by realizing that indicators can be classified in many different ways and by identifying types of indicators that reflect the aspects of health care delivery we wish to measure. Ideally these concepts should be capable of capturing the Donabedian Model (Donabedian 2005). They can be measures of structure (the tools, resources, and organizational components), processes (activities that connect patients, physicians, and staff), and outcomes (results), either as generic measures relevant for all diseases, or disease-specific measures that describe the quality of patient care related to a specific diagnosis. CIs can be categorized according to its purpose: ratebase or sentinel; related to structure, process or outcome; generic or disease specific; type of care (preventive, acute or chronic); screening, diagnosis, treatment and follow-up. The six aims of improvement, identified by the IOM, can also be used to categorize CIs (Medicine 2001), as well as those from the WHO, described above. The decision as to which indicator is selected depends on the question we are trying to answer. For each concept, there are several different indicators that can be tracked, as exemplified in table 4. Table 4: Example of CIs concept Concept Potential Indicators for this process Care of emergency acute upper bleeding patients  The total number of patients  The ED transfer rate  The percentage of ED patients admitted as inpatients  The patient wait time to endoscopy procedure After selecting a specific indicator, we create an operational definition. The next step is to develop a data collection plan; there are several important data collection issues that require some elaboration, most notably stratification and sampling. Stratification is the separation and classification of data according to selected identifiers. The objective of stratification is to create categories within the data to discover patterns that would not otherwise be observed if the data were aggregated together (e.g. day of the week; time of the day; time of the year; severity of the patient; referral vs. non-referral). So, if we want to organize our indicator development form we must be able to answer some questions: 1) / Chapter II - Background 74 What process or outcome does this indicator measure?; 2) Why do I want to measure this indicator?; 3) Which objective does it satisfy?; 4) Which dimension of quality does it cover?; 5) Are there literature references for this indicator?. A frequently asked question is whether structure, process or outcome is the best measure of quality of care. Evaluations of quality that rely only on structural elements implicitly assume that well-qualified people working in wellorganized settings will provide highquality care. Good outcomes can result even when the care is clearly deficient. The reverse is also possible: although the care is excellent, the outcome may not be a good one. Ultimately what a particular outcome tell us about quality of care depends crucially on whether the outcome can be attributed to the care provided. In other words, we have to examine the link between the outcome and the antecedent process and determine whether the care provided was appropriate and whether it was provided skillfully. Once it has been established that certain procedures used in specific situations or for certain patients are clearly associated with good results, the presence or absence of these procedures for such patients or situations can be accepted as evidence of good or bad quality. Such evidence-based structural or process indicators may be referred to as ‗outcome validated‘ and represent direct measures of quality. Process indicators are especially useful when: QI is the goal of the measurement process; an explanation is sought for why specific providers achieve particular outcomes; short time frames are necessary; performance of low volume providers is of interest; and when tools to adjust or stratify for patient factors are lacking. Comparisons of process data are easier to interpret and more sensitive to small differences than comparisons of outcomes data. A process indicator can measure whether or not an upper bleeding patient receives the right medication, whereas 30-day mortality rates may be difficult to interpret (Palmer 1998; Mainz 2003). Palmer suggests that outcomes data are useful if : outcomes can be measured that are affected by health care; long time-frames are possible; performance of whole systems should be studied; or if a high volume of cases is available. Outcomes data are most useful for tracking care given by high-volume providers over long periods of time, and for detecting problems in implementation of processes of care (Palmer 1998) A reasonable strategy is to select measures that meet the needs of each particular condition or treatment; sometimes these will be structure or process measures, and sometimes outcomes measures. More often, they will be a combination of the two (Mainz 2003). / Chapter II - Background 75 In practice, to assess quality, using structure, process or outcome measures, we need to know what constitutes good structure, good process, or good outcomes. We need criteria and standards for those aspects of care. Criteria refer to specific attributes that are the basis for assessing quality. Standards express quantitatively what level the attributes must reach, to satisfy the expectations about quality. Quality measurement and improvement in endoscopy are essential for the quality of care in gastroenterology. Publications have primarily addressed issues of technical quality and patient safety (Baron, Petersen et al. 2006; Cohen, Safdi et al. 2006; Faigel, Pike et al. 2006; Jacobson, Chak et al. 2006; Rex, Petrini et al. 2006; Axon 2009; Coe, Raimondo et al. 2009; Colton and Curran 2009; Crispin, Birkner et al. 2009; Faigel and Cotton 2009; Ho and Wiersema 2009; Lieberman, Faigel et al. 2009; Polkowski, Gerke et al. 2009; Rembacken 2009; Siddiqui, Yang et al. 2009; Al-Haddad, Gill et al. 2010). The first guidelines or position statements on various aspects of quality and safety indicators have been developed by the British Society of Gastroenterology, the American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology, the World Organization of Digestive Endoscopy, the International Agency for Research in Cancer and the Canadian Association of Gastroenterology. These guidelines are all procedure based. They don´t address patients needs and don't provide a framework for adoption in the overall context of endoscopic services. For example, in the British guidelines, quality and safety have been separated to highlight the difference between the benefits (quality) and harm (safety) of endoscopic procedures. The indicators have been separated further into two broad categories: relatively fixed items: structure, process and staffing and more dynamic indicators: auditable outcomes and quality standards. However, recognition of the need for great patient focus in health care has led to include other dimensions of quality: patient access to procedures; the appropriateness and timeliness of procedures, and patient's comfort and satisfaction. The most recent guidelines, like the Canadian ones, are patient-centered and try to cover the patients' journey (Armstrong, Barkun et al. 2012). A comprehensive quality assurance program should incorporate quality across all aspects of endoscopy. One good example is the Global Rating Scale (GRS) which has been implemented in endoscopy departments throughout England and validated in Netherlands (Sint Nicolaas, de Jonge et al. 2012). The development of the GRS was prompted by the introduction of a colorectal cancer screening programme and by shortcomings in the quality of endoscopy (Bowles, Leicester et al. 2004; Radaelli, Meucci et al. 2008). / Chapter II - Background 76 A national roundtable on health care quality, established in 1995 by the IOM stated that a comprehensive approach to measuring the quality of care requires attention to three different kinds of quality problems: too much care [overuse], too little care [underuse], and misuse [flaws and errors in technical and interpersonal aspects of care] (Medicine 1999): a) Too Much Care: unnecessary or inappropriate care: an example of overuse include the excessive or unnecessary use of emergency endoscopy procedures; this practice may result in still further procedures (laboratory) and activities (patient transfer) in a cascade of interventions that might have been avoided and that might make patients vulnerable to harmful side effects with wasting of money and resources, that could be put to more effective use. b) Too Little Care: underuse of needed, effective, and appropriate care: many studies have demonstrated the large gap between what is known to be effective care and what patients actually receive, as mentioned before about variability in clinical practice. c) Misuse: shortcomings in technical and interpersonal aspects of care: inferior care results when the performance of health care professionals or support systems is inadequate. Examples include preventable endoscopic complications or failure to monitor or follow up those complications. In 2011, Katharine A. Germansky and Daniel A. Leffler, realizing that only endoscopy has been the focus of QI work, reviewed a variety of areas in clinical gastroenterology where, existing guidelines and published data suggest both, the need and viability of active quality assurance measures (Germansky and Leffler 2011). The authors suggested that as mortality rates for gastrointestinal bleeding remained stubbornly high, mortality rates should be monitored and case fatalities reviewed, ideally by a multidisciplinary team, in order to identify areas for improvement. Indeed, the authors referred to clinical audit. Clinical audit is a cyclical process, where standards are agreed and data collected. Findings from the analysis of collected data show whether or not standards are being met. If they are not being met, changes are planned and implemented, and data are collected for a second time and analyzed to see if any improvements have resulted from these changes. The definition of clinical audit, endorsed by the National Institute for Clinical Excellence is: clinical audit is a QI process that seeks to improve patient care and outcomes through a systematic review of care against explicit criteria and the implementation of change. Aspects of the structure, processes, and outcomes of care are selected and systematically evaluated against explicit criteria. Where indicated, changes are implemented at an individual, team, or service level and further monitoring is used to confirm improvement in healthcare delivery (NICE 2002). This means, the systematic approach encouraged by Deming. / Chapter II - Background 77 Gastrointestinal endoscopy is a complex diagnostic and therapeutic activity that demands a high level of skill and knowledge on the part of the operator. However, high-quality endoscopy requires more than a skilled operator. The delivery of high-quality endoscopy services, in a cost-effective manner consistent with the broader needs of a health care system, requires a formal QI framework that addresses all aspects of endoscopy service delivery: from the patient‘s initial contact with a health care provider through to documentation of outcomes. Recognition of the patient as the focus of the endoscopy process provides a structure for integrating the efforts needed to ensure a high-quality service. So, measurement of health care quality serves a range of objectives, including the following: providing data to inform QI efforts; to know if a facility meets previously established standards; identifying and possibly eliminating substandard performance; monitoring and reporting information about changes in quality of care over time; and addressing the health needs. In general, either processes or outcomes may be valid measures of quality. For an outcome to be a valid measure of quality, it must be closely related to processes of care that can be manipulated to affect the outcome. Likewise, for a process to be a valid measure of quality, it must be closely related to an outcome. Each one plays a part in quality measurement. Structural measures of quality typically include the characteristics of the resources in the health care system, including individual practitioners, groups of practitioners, organizations and systems of care, geographic location, and accessibility of services. They are measures of the presumed capacity of the practitioner or provider to deliver quality health care. Peter Cotton drew attention to this problem some years ago, in the endoscopy setting (Cotton 2011). Endoscopists cannot work without good facilities, equipment, and a team of well-trained and motivated staff; so, one point that must attract our attention relates to the metrics of quality in endoscopy units. Measures of performance may include interpersonal aspects of care, service, timeliness, and convenience. Technical aspects of care include the timeliness and accuracy of diagnosis, the appropriateness of therapy, complications, and mishaps during treatment, and coordination of care across delivery settings. Errors in carrying out the complex series of steps often involved in patient care may contribute to preventable deaths or failures. Health outcomes include the traditional measures of survival (expressed as risk-adjusted mortality), unintended effects of treatment (e.g., perforation), and the relief of symptoms. Such measures may be specific to a given health problem and may focus on other outcomes (e.g., thirty-day survival, complications from disease, or free of bleeding after successful therapeutic endoscopy). An outcome measurement is in / Chapter II - Background 78 some ways the ultimate form of quality measurement because, what interests most people is whether care has improved the patient's health. Nevertheless, the pitfalls are great; to be useful for QI, outcomes data need to provide information with a high level of clinical detail and be provided in a sufficiently clear manner that providers can know what processes must be changed. Many, in the health care system have begun to apply a model of QI called continuous QI or total quality management. One assumption of this model is that the health care organizations and systems within which professionals practice can always improve. One way to acquire this improvement is to set up continuous monitoring systems that alert the organization when performance in some area is slipping or to confirm that efforts at improving care are succeeding, or both. Assessing the effectiveness of health care, clearly requires the measurement of health improvement—the difference in health with and without some intervention. Most countries, like Portugal, face high demands on their health care systems and a limited budget to meet these demands. Clinicians often face situations where there is information demonstrating the benefits from an intervention or treatment, but, there is still little context in which to understand how much their patients will value these benefits and whether the benefits are significant enough to merit expending scarce resources. Furthermore, it could be argued that it is an ethical responsibility to consider these issues as the savings on spending could be directed to other areas of health with greater efficiency. However, the need to assess the ―economic‖ gain from alternative forms of care is reflected in the continuing development of economic evaluation methods and the increasing numbers of studies with health economic input. Compilers of clinical practice guidelines are also placing more emphasis on economic data. Economic evaluations of interventions are central to informing the advice and decisions issued by organizations such as the UK‘s National Institute for Clinical Excellence. That is, organizations are concerned with issues of cost-effectiveness and cost-benefit. One of the foremost organizations in the pursuit of rigorous evidence on the effectiveness of interventions is the Cochrane Collaboration – an international organization with the aim of improving the effectiveness of health care throughout the world by preparing, maintaining and making accessible systematic reviews of the effects of health care. Economic assessments have become an integral part of policy decisions on healthcare, because expenditures on health care in developed countries have risen faster. Consequently, health-care expenditure has been consuming an ever-larger share of the / Chapter II - Background 79 total economy, and politicians have to balance the optimum level of expenditures on health care. Economic evaluation can assess whether one particular intervention is worth undertaking compared to another intervention (or compared to doing nothing). Economic evaluation analyzes whether the additional benefits of an intervention are greater than the additional costs. In economic analyses, costs are typically categorized as ―direct medical‖, ―direct non-medical‖, and ―indirect costs of lost productivity‖. In financial or accounting analyses, costs are classified differently, as ―variable‖ or ―fixed‖. Variable costs, such as the physician‘s time and drugs administered, vary dependent on the numbers of cases treated, whereas fixed costs do not vary in the short-to medium term and are unlikely to change with any fluctuations in the number of cases (e.g., the cost of a building). Some health economists do use accountancy terms such as ―fixed costs‖ but this is not a serious problem so long as the costs that are included are those appropriate for the perspective chosen and reflect the opportunity costs (Meltzer 2001). The maximum possible reduction in a disease due to the use of an intervention is termed the efficacy of the intervention. Efficiency evaluates how well resources are used to achieve a desired outcome. It has a number of different aspects: allocative efficiency measures the extent to which resources are allocated to the groups or individuals who can benefit most. For example, the benefits of urgent endoscopy provided in the first two hours to high-risk patients are far in excess of the benefits that arise when it is done in low-risk patients; allocative efficiency therefore requires the high-risk patients to be targeted as a priority, resulting in an improved level of health associated with very early emergent endoscopy; technical efficiency measures either the extent to which resources are combined to achieve maximum outcome, or alternatively the minimum amounts of resources that are combined to achieve a given outcome (for example, identifying the least expensive way to effectively treat a bleeding peptic ulcer; in this case, doing an unnecessarily second-look endoscopy or long courses of drugs or unnecessarily expensive drugs implies the existence of technical inefficiency. Since the objective of economic appraisal is to seek efficient and equitable uses of resources it is important that all potentially efficient and equitable options should be examined. The options examined have to be selected as being those considered to offer the greatest potential. This again emphasizes how economic appraisal builds on epidemiological evaluation and clinical trials. For example, an economic appraisal of an out-of-hours endoscopy program in the North of Portugal, could examine the alternatives of: no program; a large regional program; a program for old people only; for one city; for every city; for three cities; a program for one or two year; a program phased over several years. Ultimately the appraisal objective is to seek social efficiency and equity. However, when there is a constraint on the resource budget, seeking the most technically efficient / Chapter II - Background 80 (maximum benefit) way of spending will be the objective. Where there is a fixed benefit or health effect to be achieved, the objective is to seek the most technically efficient—i.e. least cost—way. Economic evaluation uses information on the costs and outcomes of different treatments to guide choices among competing demands for health care resources. We have limited resources, so have to choose between health services; health economics offers systematic ways to guide these choices. The three main methods used to assess the economics of an intervention in healthcare are: cost-benefit analysis (CBA), costeffectiveness analysis (CEA), and cost-utility analysis (CUA). The central purpose of CEA is to compare the costs and the values of different health care interventions in creating better health and longer life. Many new medical devices, procedures, diagnostic tests, and prescription drugs are expensive; cost-effectiveness analysis can help to evaluate whether the improvement in health care outcomes justifies the expenditures relative to other choices. This understanding of the costs and outcomes of comparative interventions is essential for decision makers to make informed decisions about using health care resources efficiently. Questions of technical efficiency are addressed using CEA. The CBA in health care is the analysis of health care resource expenditures relative to possible medical benefit. This analysis may be helpful and necessary in setting priorities when choices must be made in the face of limited resources. This analysis is used in determining the degree of access to, or benefits of, health care to be provided. A particular form of CEA that is becoming more widespread in health care is where the benefits/health effects are expressed in terms of ‗quality-adjusted-life-years‘ (QALYs) gained. This particular form of CEA is called CUA. In CUA the health effects of a project are expressed on a 0–1 scale of quality adjusted life for each time period, and the tangible outcomes/resource consequences in monetary terms. The overall effects of projects are set in terms of ‗cost per QALY gained‘. In conclusion, quality of care is a complex interaction between processes of care, clinical and patient oriented health outcomes and the productivity of a health care system (figure 4). / Chapter II - Background 81 Figure 4: Factors determining the outcome of care in health care delivery Adapted from International Journal for Quality in Health Care 2003 Chapter II - Background 89 II. BACKGROUND IIb. Non-Variceal Acute Upper Gastrointestinal Bleeding IIb1. Occurrence and Mortality Trends AUGIB is the commonest cause of acute hospital admission to gastroenterology and therefore has a large impact on the acute medical admission workload. Changes in management have been shown in randomized controlled trials to improve outcome from gastrointestinal hemorrhage, but the largest observational studies of mortality trends following upper gastrointestinal hemorrhage report no improvement in overall mortality over the last 2 decades (van Leerdam, Vreeburg et al. 2003; Thomopoulos, Vagenas et al. 2004; Targownik and Nabalamba 2006; Loperfido, Baldo et al. 2009). The populationbased study of patients hospitalized because of gastrointestinal complications in 10 general hospitals between 1996 and 2005 in Spain, performed by Lanas et al. (Lanas, Garcia-Rodriguez et al. 2009), demonstrated a progressive change in the overall picture of gastrointestinal bleeding (GI) events leading to hospitalization, with a clear decreasing trend in upper GI events and a significant increase in lower GI events, causing the rates of these two GI complications to converge. Overall, mortality has also decreased, but the inhospital case fatality of upper or lower GI complication events has remained constant. According to the author, it will be a challenge to improve future care in this area, as well as reducing their associated mortality. Another study, from Netherlands, also examined time trends in incidence and outcome of upper GI bleeding (van Leerdam, Vreeburg et al. 2003). They reported that incidence decreased from 61.7/100,000 in 1993/94 to 47.7/100,000 persons annually in 2000, corresponding to a 23% decrease in incidence after age adjustment (95% CI = 15-30%). The incidence was higher among patients of more advanced age. However, rebleeding (16% vs. 15%) and mortality (14% vs. 13%) did not differ between the two time periods. Also, among patients with ulcer bleeding, rebleeding (22% vs. 20%) and mortality (15% vs. 14%) did not differ between the two time periods. Increasing age, presence of severe and life-threatening comorbidity, and rebleeding were associated with higher mortality. Another study from Greece, compared the etiology and clinical outcome of AUGIB, between two distinct periods, during 15 years: 668 patients hospitalized with the problem in 1986-1987 were compared to 636 patients with AUGIB in 2000-2001. Overall mortality was also reduced from 5.2% to 3.1% and in peptic ulcer bleeding patients from 3.3% to 2.4%, respectively, but the differences were not statistically significant (Thomopoulos, Vagenas et al. 2004). Also a Greek study, Chapter II - Background 90 estimated the incidence of AUGIB and peptic ulcer bleeding (PUB) in two different periods, 1995 and 2005. A reduction in the incidence of AUGIB from 162.9/100,000 population in 1995, to 108.3/100,000 population (rate ratio=0.49, confidence interval 95%=0.37-0.63) in 2005 and in the incidence of PUB from 104.8/100,000 population to 72.5/100,000 (rate ratio=0.49, confidence interval 95%=0.35-0.68) were, respectively, observed. The authors concluded that although the incidence of AUGIB significantly decreased, patients were older with more comorbidities, and mortality remained unchanged (Theocharis, Thomopoulos et al. 2008). The French also evaluated the main changes in characteristics, practices and outcome between 1996 and 2000 in patients admitted for an acute upper gastrointestinal hemorrhage (variceal and non-variceal hemorrhage); they observed a significant decrease in AUGIB mortality in the whole group (11.7 versus 7.2%; P=0.03), and particularly in the subgroup of cirrhotic patients (19.5 versus 11.1%; P=0.05) whatever the source of their bleeding (Di Fiore, Lecleire et al. 2005). A retrospective non-randomized clinical study performed during 2011 that took place at the Regional Institute of Gastroenterology and Hepatology in Cluj Napoca, revealed an important decrease in the need for urgent haemostatic surgery despite a relatively constant general mortality rate. Comparing data from 2011 with data from 2002 in the same hospital, they noticed a decrease by half for urgent haemostatic surgery in cases of non-variceal bleeding. In 2002, the need for urgent haemostatic surgery was 7.9% for non-variceal bleeding with a drop from 17% in 1989. In 2011, need for urgent surgery was 3.68%. The mortality rate was similar to previously data, reaching approximately 10%, remaining constant (Botianu, Matei et al. 2013). A single-center study from Italy, compared 587 patients who presented with AUGIB during the 1983-to-1985 period, with 539 patients in the 2002-to-2004 period. The overall incidence of AUGIB decreased from 112.5 to 89.8 per 100,000/y, which corresponds to a 35.5% decrease after adjustment for age (95% CI, 24.2%-46.8%). The age standardized incidence of ulcer bleeding decreased by 41.6% (95% CI, 27.2%-56%); the decrease occurred only in people younger than 70 years of age. Rebleeding rates decreased from 32.5% to 7.4% (P < .001) and surgery from 10.2% to 2.0% (P < .001). Overall mortality decreased from 17.1 to 8.2 per 100,000/y, which corresponded to a 60.8% decrease after adjustment for age (95% CI, 46.5%-75.1%). The age standardized mortality rate for ulcer bleeding decreased by 56.5% (95% CI, 41.9%-71.1%). The explanation for these data was that, advances in medical practice in recent decades have influenced the etiology and management of AUGIB (Loperfido, Baldo et al. 2009). In 2007, a study from Canada, confirmed the decrease in incidence from NVAUGIB; between 1993 and 2003, NVUAGIB incidence decreased from 77.1 cases to 53.2 per 100,000/y for the broad definition, and from 52.4 to 34.3 cases per 100,000/y for the narrow definition (ICD-9/ICD-10-based definition). Chapter II - Background 91 Although the proportion of NVAUGIB subjects requiring surgical intervention declined over the 10 years from 7.1% to 4.5%, the mortality rate remained steady at approximately 3.5%; but they only identified deaths that occurred before discharge (Targownik and Nabalamba 2006). The low mortality identified in this study (3.5%) is similar to other North American (Zhao Y.) and Mediterranean (Lanas, Garcia-Rodriguez et al. 2009) studies but is much lower than the European studies previously cited (van Leerdam, Vreeburg et al. 2003; Di Fiore, Lecleire et al. 2005; Loperfido, Baldo et al. 2009; Botianu, Matei et al. 2013). So, the studies with mortality reduction did not report variceal and non-variceal hemorrhage mortality trends separately or trends in different age and comorbidities. Other non-variceal hemorrhage studies from Spain, The Netherlands, Greece, Romania and France, with the exception of the Italian one, did not identify reductions in non-variceal inpatient mortality. Although these were large studies, none of them identified deaths that occurred after discharge because outcome was just analyzed in terms of in-hospital death. More recently, a case control study, estimated trends in 28-day mortality in England following hospital admission for gastrointestinal hemorrhage. They used a case-control study design to analyze data from all adults administered to a National Health Service hospital, for upper gastrointestinal hemorrhage, from 1999 to 2007 (n=516,153). Cases were deaths within 28 days of admission, and controls were survivors to 28 days. The 28day mortality was derived from the linked national death register. A logistic regression model was used to adjust trends in non-variceal and variceal hemorrhage mortality for age, sex, and comorbidities and to investigate potential interactions. The mortality in this study improved right up to the end of the study period. The authors clarified some reasons for the reduction in mortality: there were similar reductions in mortality whether or not an endoscopy was recorded and for all associated diagnoses, implying that endoscopic therapy was not a major contributor to the reduction in mortality; that improvement in standard non-endoscopic care has led to improved survival, such as the routine administration of intravenous proton pump inhibitor infusions, the routine use of risk scoring, the implementation of standardized clinical guidelines, and the subsequent local auditing of practice (Palmer 2002; Gralnek, Barkun et al. 2008; 2010; Barkun, Bardou et al. 2010). It is important to notice that differences in practice may confound comparisons between countries. Even in the same country, variability in patient's management is observed (Hearnshaw, Logan et al. 2010). Nevertheless, an European Survey of Nonvariceal Upper Gastrointestinal Bleeding (ENERGIB) concluded that differences in outcomes of Chapter II - Background 92 NVAUGIB reported across countries did not seem to be due to differences in clinical management or health organizations, at least within a European setting (Lanas, Aabakken et al. 2011). ENERGIB was an observational, retrospective cohort study carried out across multiple centers in seven countries (Belgium, Greece, Italy, Norway, Portugal, Spain and Turkey). A target sample size of 400 patients per country was established and 123 centers participated in the study, with the following distribution per country: Belgium (26 centers), Greece (10), Italy (11), Norway (16), Portugal (12), Spain (24) and Turkey (24). A total of 2664 patients were included in the study, and 2660 patients were eligible for the statistical analyses. They evaluated a number of variables possibly associated with outcomes of NVAUGIB including clinical predictors, management strategies and healthcare resource utilization in a 'real-world', European, clinical practice setting. This report focused on the predictors of poor outcomes of NVAUGIB in terms of bleeding continuation/re-bleeding and mortality. Overall, 12.3% of patients experienced bleeding continuation/re-bleeding within 30 days of the initial NVAUGIB episode. Continued bleeding was observed in 7.3% of patients, while 10.5% of patients experienced rebleeding within 30 days. The proportion of patients undergoing surgery (other than endoscopy) to control bleeding was low, at 3.3%. The mortality rate within 30 days of the bleeding event was 5.2%. The ENERGIB study therefore confirmed that mortality associated with NVAUGIB has not decreased substantially in recent years, despite advances in endoscopic and pharmacological therapies. There are some methodological limitations in this retrospective study that must be considered: all patients were treated according to the standard clinical care protocol at each participating study site; the practice of retrospective collection of data through clinical records, make it particularly difficult to check and unreliable. Other factors that have been linked to fatality rates in AUGIB such as, social deprivation or day of the week of hospitalization, have not been considered (Lanas, Aabakken et al. 2011). It is difficult to understand how different processes produced similar outcomes. If this was the question this time round, the answer came afterwards. In 2012, Lanas et al. tackled the problem of variability in the management of NAVUGIB in Europe by effectively identifying the processes (Lanas, Aabakken et al. 2012). The results showed a wide between-country variability in the area and specialty of the NAVUGIB management team and unit transfer rates after the initial hospital assessment. The mean time from admission to endoscopy was <1 day only in Italy and Spain. Wide variation in the use of pre-endoscopy (35.0-88.7%) and relatively consistent (86.5-96.0%) post-endoscopic pharmacological therapy rates were observed. There was substantial by-country variability in the rate of therapeutic procedures performed during endoscopy (24.9-47.6%). NVAUGIB-related healthcare resource consumption was high and variable (days hospitalized, mean 5.4-8.7 days; number of Chapter II - Background 93 endoscopies during hospitalization, mean 1.1-1.7). The authors concluded that ENERGIB demonstrated that there were substantial differences in the management of patients with NVAUGIB episodes across Europe, and that in many cases the guideline recommendations for the management of NAVUGIB were not being followed. A total of 404 Portuguese patients from twelve hospitals, with NVAUGIB were included in ENERGIBE study, with a mean age of 68.5±17.1 years. The clinical risk score evaluated by the expected clinical risk scales (Rockall, Blatchford or ASA scales) was not registered in any of the Portuguese patients‘ clinical records. The mortality rate was 4.8% and, only in four cases, was directly related to the bleeding episode. Data were collected retrospectively from patients‘ medical records and so, many data were missed, like the endoscopy timeframe (Fonseca, Alves et al. 2012). Another retrospective Portuguese study, analyzed data from 597 patients admitted with AUGIB between August,1974 and August,1979 and reported a mortality rate of 10% and 6% for AUGIB and NVAUGIB, respectively (Carlos Sofia 1981). A prospective, six year study, to evaluate the adequacy of a simple "Numerical Risk Score", proposed by the National Audit of Acute Upper Gastrointestinal Hemorrhage (United Kingdom), for a population of 372 high risk patients admitted to a Gastroenterological Intensive Care Unit with peptic ulcer bleeding, was conducted in Portugal and published in 1999. The mortality rate was 3,4%, 9,7% and 19,4% for ward inpatients, intensive care patients and surgery patients, respectively (José Manuel Romãozinho and Ernestina Camacho 1999). I am unaware that there are more studies published in Portugal. The results of 1402 surveys of emergency physicians, internists, and gastroenterologists practicing in USA hospitals were as follows: there was no difference in the application of the quality indicators by specialty or clinical position. Among all physicians, 53% had ever heard of and 30% had ever used a risk score. More gastroenterologists than nongastroenterologists had heard of (82% vs. 44%, P<0.001) and used (51% vs. 23%, P<0.001) a risk score. There was no difference between attending physicians and trainees. Gastroenterologists and attending physicians more often cited lack of utility as a reason to not use risk scores, whereas non-gastroenterologists and trainees more often cited lack of knowledge. They concluded that, although the agreement with AUGIB initial management guidelines was high but adherence-especially pertaining to the use of risk scores was low (Liang and Saltzman 2014). So, in general, the failure to demonstrate a clinical improvement in NVAUGIB may be due to, either clinical guidelines not being followed or patient‘s characteristics have changed. Chapter II - Background 94 This latter explanation, with increasing age and comorbidity has been proposed as the likely explanation. For instance, if in some acute emergencies, such as heart attacks, the most common cause of death relates to the associated cardiovascular disease, but in other emergencies, such as stroke, death is commonly associated with other causes, such as cardiovascular disease and respiratory infections (Bronnum-Hansen, Jorgensen et al. 2001; Vernino, Brown et al. 2003). However, despite NVAUGIB being one of the most common gastroenterology reasons for admission in acute medicine, the outcomes of patients who have experienced a NVAUGIB episode are poorly understood in the context of the process of care. Therefore, to identify which interventions may possibly reduce mortality, we must analyze the impact of several factors in health care delivery system, which may vary from system to system. CHAPTER II BACKGROUND IIa. Quality in Health Care IIa1. Definition and Dimensions of Quality IIa2. Quality Assessment and Improvement IIa2.1. The History of Quality Improvement IIa2.2. Assessing and Measuring Quality in Healthcare IIb. Non-Variceal Acute Upper Gastrointestinal Bleeding IIb1. Occurrence and Mortality Trends IIb2. Interventions That Work IIb3. Interventions That Need More Study: controversies and areas of uncertainty / Chapter II - Background 97 II. BACKGROUND IIb. Non-Variceal Acute Upper Gastrointestinal Bleeding IIb2. Interventions That Work As we have shown, although some data suggest a reduction in the incidence, the clinical burden and economic costs of NVAUGIB remain high (van Leerdam, Vreeburg et al. 2003; Ahsberg, Ye et al. 2011; Lanas, Garcia-Rodriguez et al. 2011). The initial assessment is to determine whether the patient requires urgent intervention (e.g., endoscopic, surgical, transfusion) or can undergo delayed endoscopy or even be discharged to outpatient management. Although numerous factors from the patient history, physical examination, and initial tests have been examined for an association with a need for intervention, no single factor is sufficiently predictive of NVAUGIB severity to be used for triage. The most predictive individual factors are a history of malignancy or cirrhosis, (Adamopoulos, Baibas et al. 2003) presentation with hematemesis, (Adamopoulos, Baibas et al. 2003; Aljebreen, Fallone et al. 2004) and signs of hypovolemia including hypotension, (Stoltzing, Ohmann et al. 1991; Adamopoulos, Baibas et al. 2003) tachycardia and shock, and a hemoglobin <8 g/dL. (Adamopoulos, Baibas et al. 2003; Aljebreen, Fallone et al. 2004) Some factors, such as a history of aspirin or no steroidal anti-inflammatory use, may not be useful for immediate disposition but are still important to assess for future management [e.g., if peptic ulcer disease] (Stoltzing, Ohmann et al. 1991). Patients who have significant comorbidities may require admission regardless of the severity of the NVAUGIB. In fact, many risk factors are associated with bleeding, and these must be addressed. Endoscopic intervention reduces the rate of rebleeding, the need for surgical intervention, and mortality in high-risk patients. / Chapter IIBackground 104 The Optimal Timing For Endoscopy Endoscopy has a clearly-defined role in the primary management of NVAUGIB (Hwang, Fisher et al. 2012). The endoscopic haemostatic therapy for NVAUGIB is indicated for patients having ulcers with high risk bleeding stigmata such as active bleeding or no bleeding visible vessels. The endoscopist can choose the haemostatic method according to the type, size, ulcer base characteristics, and location of the lesion. Injection therapy using epinephrine, ethanol, or hypertonic saline, thermal coagulation using contact and noncontact devices has been common choices in NVAUGIB with good outcomes. Endoscopic mechanical modalities currently available can provide secure bleeding control in most cases. Endoscopic hemostasis using a combination of currently available methods is preferred to monotherapy, especially to injection therapy alone, considering the synergistic effect of each modality having different mechanism of action. Appropriate indications for some therapeutic endoscopic interventions are well established and there has recently been increasing consensus regarding when and how the various methods for controlling bleeding should be deployed. But, although timing of endoscopy plays an important role in the diagnosis, risk stratification and treatment of AUGIB, the optimal timing for this investigation is still unclear. Service provisions for out-of-hours endoscopy are highly variable, and offering 24-hour endoscopy across all institutions may have serious economic implications. Evidence-based consensus guidelines recommend endoscopy within 24h (Barkun, Bardou et al. 2010; Laine and Jensen 2012). Very early endoscopy [<12 h] when compared with early endoscopy [>12 h and < 24 h] does not seem to confer any additional benefits in terms of rebleeding, need for surgery, or mortality in unselected patients with NVAUGIB based on randomized trial findings (Lin, Wang et al. 1996; Bjorkman, Zaman et al. 2004; Lim, Ho et al. 2011). However, Lim et al., suggested, using observational data, that endoscopy within 13 h of presentation was associated with a lower mortality in selected high-risk patients, defined as GBS > 12 (Lim, Ho et al. 2011). So, although some authors propose that endoscopy should be carried out within 12 h in acutely ill patients, this is supported by limited data (Lin, Wang et al. 1996; Lim, Ho et al. 2011) and is currently controversial (Barkun, Bardou et al. 2012). Furthermore, early endoscopy may identify those patients who can be safely discharged immediately after endoscopy, or, when combined to other factors, promptly and safely discharge patients already hospitalized (Forssman 1976; Moreno, Jaurrieta et al. 1998; Chaparro, Barbero et al. 2010; Rotondano, Cipolletta et al. 2014). In fact, early endoscopy within 24 h of presentation following successful resuscitation is recommended for patients with NVAUGIB (Barkun, Bardou et al. 2010). A recent review aimed to evaluate the / Chapter IIBackground 105 optimal timing of early endoscopy by examining the findings of randomized clinical trials and retrospective cohort studies that used comparable outcome measures and have been reported in the literature (Tsoi, Ma et al. 2009). Of the 1,498 studies they have identified through database searches, the discussion was based in the review of three randomized, controlled trials (Lin, Wang et al. 1996; Lee, Turnipseed et al. 1999; Bjorkman, Zaman et al. 2004) and five retrospective cohort studies (Cooper, Chak et al. 1998; Cooper, Chak et al. 1999; Schacher, Lesbros-Pantoflickova et al. 2005; Tai, Huang et al. 2007; Targownik, Murthy et al. 2007). They found great heterogeneity in the study design, follow-up period, endoscopic therapy and adjuvant therapy in these eight studies. One crucial factor in the evaluation of timing for early endoscopy is whether hemodynamically unstable patients were excluded from the studies. Among the eight trials, two specifically excluded hemodynamically unstable patients (Lee, Turnipseed et al. 1999; Bjorkman, Zaman et al. 2004). Five studies included both stable and unstable patients (Lin, Wang et al. 1996; Cooper, Chak et al. 1998; Cooper, Chak et al. 1999; Schacher, Lesbros-Pantoflickova et al. 2005; Tai, Huang et al. 2007) and one study included only hemodynamically unstable patients (Targownik, Murthy et al. 2007). They concluded that early endoscopy (less than 2 to 6 h) showed no improvement in clinical outcomes compared with a delayed approach [less than 24 to 48 h] (Tsoi, Ma et al. 2009). This has also been reflected by a large prospective UK audit, that demonstrated that endoscopy within 12 h did not affect mortality or the need for surgery, but led to a decreased length of stay(Jairath, Kahan et al. 2012). Concluding, we need to focus on tools which address major concerns like effectiveness, safety and costs, in order to achieve, from medical, endoscopic, and pharmaceutical intervention, improvement in outcomes and reduce medical costs, by reducing rebleeding, length of hospital stay and the need for surgical procedures. We have already set out our view of these issues (Pedroto, Dinis-Ribeiro et al. 2012). CHAPTER III RESEARCH METHODOLOGY IIIa. Setting IIIb. The Process IIIc. Patients and Data Analysis IIId. Statistical Analysis CHAPTER III RESEARCH METHODOLOGY IIIa. Setting IIIb. The Process IIIc. Patients and Data Analysis IIId. Statistical Analysis / Chapter III - Research Methodology 111 URGE NORTH Figure 5: The North of Portugal and URGE localization III RESEARCH METHODOLOGY IIIa. Setting From January 2010 to December 2012, a prospective observational study was conducted at the endoscopy unit of Centro Hospitalar do Porto (CHP), a 820-bed acute care, university hospital, serving, as an out-of-hours endoscopy center, an estimated population of 3.7 million (one third of the national population), with about 38 percent of the national youth population concentrated in the region (figure 5). The northern region includes eight sub-regions and an area of about 21.278 km² (24% of the continent). Since October 2006, in CHP, 30 consultant trained gastroenterologists from eight hospitals and sixteen skilled assistant staff from the endoscopy unit [eight nurses and eight endoscopy technicians] were integrated as the emergency team, everyday from 8 pm to 8 am; they are responsible for handling all gastroenterology emergencies, especially those requiring urgent endoscopy. The objectives of the URGE are: to provide phone consultations during the night; to provide consultations on site and endoscopy. URGE receives around 800-1000 patients/year, being around 53% of the patients acute upper bleeders; a non-variceal cause accounts for approximately 52% of these. Each institution is accountable for the / Chapter III - Research Methodology 112 remuneration for out-of-hours gastroenterology physician work, except for the assistant staff [nurse and endoscopy technician] that is the sole responsibility of the endoscopy unit of CHP. In this way, all are allocating human and financial resources. CHP has eight emergency teams and quarterly, the head of the gastroenterology department from five hospitals, is responsible for sending to the URGE coordinator the physicians rota, according to the teams which have been assigned to them; physicians from the smaller units strengthen some teams; this reflects 1 shift/physician/month. The provision of emergency endoscopy fulfills all the recommendations of the British Society of Gastroenterology. CHP has elective beds for bleeders in the acute medical or surgery units and two intensive care units. CHAPTER III RESEARCH METHODOLOGY IIIa. Setting IIIb. The Process IIIc. Patients and Data Analysis IIId. Statistical Analysis CHAPTER III RESEARCH METHODOLOGY IIIa. Setting IIIb. The Process IIIc. Patients and Data Analysis IIId. Statistical Analysis / Chapter III - Research Methodology 123 III RESEARCH METHODOLOGY IIIc. Patients and Data Analysis Data on all consecutive patients, aged 18 and over, admitted directly to the emergency department of Centro Hospitalar do Porto (ED-CHP) or transferred from another institution, were prospectively collected. Patients with a new onset of NVAUGIB [clinical evidence of overt upper bleeding on admission or a history of hematemesis, coffee ground vomiting, melena, hematochezia, or a combination of any of these within 24h preceding admission] and with an upper endoscopy performed were included. Patients were excluded if they were younger than 18 years old, if endoscopy was not performed, had chronic anemia or bled as inpatients hospitalized for an unrelated illness. Demographic, clinical and endoscopic data from patients with NVAUGIB were collected and those with other sources of bleeding were excluded. Comorbidity was defined as the presence of any of the following diseases: (1) cardiac disease including ischemic heart disease and congestive heart failure; (2) hypertension; (3) chronic liver disease; (4) chronic renal disease; (5) vascular disorders including peripheral and central vascular diseases; (6) history of stroke; (7) diabetes; (8) malignancy; (9) metastatic malignancy; (10) renal or liver transplant; (11) hereditary bleeding disorder; (12) peptic ulcer disease, complicated or not. All medication, at time of presentation, was recorded. Patient workflow was examined: time of admission at the first hospital, time of first contact to the endoscopy unit, time of arrival to the endoscopy unit, time of endoscopic procedure, time of inpatient admission, discharge or transferred back to the first hospital; endoscopic lesion and therapy; adverse events (table 8). Mortality was defined as any death occurring during hospitalization or within 30 days of the index bleeding episode and considered as bleeding related (after uncontrolled bleeding; occurring within 24h after endoscopy; during surgery for uncontrolled bleeding; adverse events during endoscopy or surgery) or non-bleeding related (comorbidity or nosocomial infections). Rebleeding was defined as recurrent haematemesis, melena, with hemodynamic instability or a decrease in hemoglobin concentration of at least 2g/L and confirmed by a second endoscopy, recurring within 30 days. Our primary variables were out-of-hours direct admissions to ED-CHP vs. out-of-hours transferred patients from another institution. / Chapter III - Research Methodology 124 Table 8: Baseline characteristics of patients and data recorded Symptoms / signs (hematemesis, melena, hematochezia) Age Gender Prior upper gastrointestinal clinical events (e.g., bleeding, perforation) Major current comorbidities Key medications (NSAIDs, antithrombotics, and antisecretory) Hemoglobin and hematocrit (at presentation) Platelets, INR, urea, creatinin Transfusions (number of units) Timing of endoscopy (hours after presentation to the first hospital: CHP or other hospital) Timing of first contact to the endoscopy tertiary referral regional endoscopy unit Timing of arrival to the endoscopy tertiary referral regional endoscopy unit Timing of admission or transfer or discharge, after endoscopy Endoscopic Lesion Stigmata of hemorrhage (Forrest classification) Endoscopic therapy Score from scoring system validated to predict outcomes (Rockall) In-hospital rebleeding 30 day Readmissions Surgery 30-day Mortality Exclusion Criteria Age under 18 years Symptoms or signs of blood loss or anemia Patients that did not undergo endoscopy for the following reasons: patients specifically categorized as terminal care patients; patients who refused or whose family refused to consent to endoscopy; patients self discharging prior to endoscopy being undertaken; patients requiring direct and urgent surgical intervention because of rapid exsanguination; patients with a specific contraindication to endoscopy; and patients who died rapidly on admission Bleeding in patients already hospitalized for unrelated disease Patients hospitalized in other clinics and presented just for endoscopy examination CHAPTER III RESEARCH METHODOLOGY IIIa. Setting IIIb. The Process IIIc. Patients and Data Analysis IIId. Statistical Analysis / Chapter III - Research Methodology 127 III RESEARCH METHODOLOGY IIId. Statistical Analysis Categorical variables were described as absolute frequencies (n) and relative frequencies (%). Median and percentiles or median and standard deviation were used for continuous variables. When testing a hypothesis about categorical variables a chi-square test and Fisher‘s exact test were used, as appropriate. In order to have a more thorough understanding of the factors associated, with mortality (in-hospital and 30 day) and rebleeding, univariate and multivariate logistic regression modeling was used. Factors that were significant in the univariate analysis at p<0.2 were included in the multivariate logistic regression models. Variables that have been previously identified to carry important prognostic significance in patients with NVAUGIH were included in the final multivariate model even if they didn‘t meet statistical significance on univariate analysis. Model discriminative power was evaluated by receiver-operator curve (ROC) curve analysis with confidence interval 95% (CI95%). The significance level used was 0.05. Statistical analysis was performed using the software Statistical Package for the Social Sciences v. 20.0. CHAPTER IV RESULTS IVa. Overall Results IVb. Main Results / Chapter IV - Results 136 Table 10: Overall results - the demand according to the year and month of the year vs. time and admission status. Total N (%) ED-CHP N (%) 8am-8pm N (%) 8pm-8am Referrals N (%) 8am-8pm N (%) 8pm-8am p Year 0.097 2010 2011 2012 Total 316 (49.2) 174 (27.1) 152 (23.7) 642 119 (46.7) 70 (27.5) 66 (25.9) 255 (39.7) 48 (42.5) 30 (26.5) 35 (31.0) 113 (17.6) 28 (50.9) 13 (23.6) 14 (25.5) 55 (8.6) 121 (55.3) 61 (27.9) 37 (16.9) 219 (34.1) Month 0.187 January February March April May June July August September October November December 57 (8.9) 61 (9.5) 68 (10.6) 57 (8.9) 59 (9.2) 64 (10.0) 62 (9.7) 51 (7.9) 44 (6.9) 39 (6.1) 53 (8.3) 27 (4.2) 22 (8.7) 29 (11.4) 25 (9.8) 20 (7.8) 20 (7.8) 28 (11.0) 21 (8.2) 14 (5.5) 17(6.7) 19 (7.5) 29 (11.4) 11 (4.3) 9 (7.8) 8 (7.1) 6 (5.3) 11 (9.7) 11 (9.7) 11 (9.7) 9 (8.0) 17 (15.0) 12 (10.6) 5 (4.4) 8 (7.1) 6 (5.3) 6 (10.9) 1 (1.8) 7 (12.7) 4 (7.3) 8 (14.5) 6 (10.9) 7 (12.7) 3 (5.5) 2 (3.6) 5 (9.1) 5 (9.1) 1 (1.8) 20 (9.1) 23 (10.5) 30 (13.7) 22 (10.0) 20 (9.1) 19 (8.7) 25 (11.4) 17 (7.8) 13 (5.9) 10 (4.6) 11 (5.0) 9 (4.1) / Chapter IV - Results 137 Concerns about determinants of resource demand have been raised and by taking this into account, we also examined changes in productivity in relation to the day of the week and weekday vs. weekend [8pm Friday to 8am Monday]. Direct in-hours admissions were less frequent on Sunday; half of the patients observed on Sunday in-hours, came from other hospitals; by contrast, Sunday and Wednesday nights, were the most busy, at the expense of transferred patients. Two thirds of the patients that were directly admitted in emergency, day or night, did it mostly during the week. On the contrary, patients transferred, day or night, showed a similar distribution, 54.5% and 56.6%, in or out-of-hours, respectively. For NVAUGIB, the less busy day of the week was Thursday (table 11). When we assayed the service provision by weekday or weekend [from Friday 8pm to Monday 8am] we observe that transferred patients are homogeneous distributed, unlike the patients directly admitted to ED-CHP; this is obviously explained by the lack of provision of endoscopy in many hospitals at weekdays, after 2pm and at weekends. Transferred patients are responsible for 42% and 36% of the endoscopic procedures at weekends and weekdays, respectively. / Chapter IV - Results 138 Table 11: Overall results - the demand according to weekday and weekend vs. time and admission status. Patients are stabilized in the nearest hospital and transferred after agreement with the consultant gastroenterologist. This was accomplished in 68% of the cases, according to the standardized questionnaire, filled out by the attending physician or the assistant nurse. Of the 642 patients, 67% we admitted during the week and 33% during weekend. More patients were admitted after-hours (52%) compared with in-hours (48%). Procedures performed after-hours were further analyzed and we observed that 54% occurred between 12am and 8am. Total N (%) ED-CHP N (%) 8am-8pm N (%) 8pm-8am Referrals N (%) 8am-8pm N (%) 8pm-8am p Day of the week 0,004 Sunday Monday Tuesday Wednesday Thursday Friday Saturday 87 (13.6) 90 (14.0) 87 (13.6) 103 (16.0) 74 (11.5) 101 (15.7) 100 (15.6) 22 (8.6) 40 (15.7) 36 (14.1) 42 (16.5) 35 (13.7) 46 (18.0) 34 (13,3) 10 (8.8) 16 (14.2) 21 (18.6) 12 (10.6) 17 (15.0) 20 (17.7) 17 (15.0) 11 (20.0) 9 (16.4) 3 (5.5) 7 (12.7) 4 (7.3) 7 (12.7) 14 (25.5) 44 (20.1) 25 (11.4) 27 (12.3) 42 (19.2) 18 (8.2) 28 (12.8) 35 (16.0) Weekday Weekend 430 (67.0) 212 (33.0) 199 (78.0) 56 (22.0) 77 (68.1) 36 (31.9) 30 (54.5) 25 (45.5) 124 56.6) 95 (43.4) 0,000 / Chapter IV - Results 139 The patient flow, lead time was examined as detailed in the next table: Table 12: Overall results - Patient Flow: Lead Time. Lead time Median Time (hours) ED-CHP 8am-8pm 8pm-8am Referrals 8am-8pm 8pm-8am P From first ED to EDCHP 15.0 6.8 0.003 Weekday 16.1 6.5 0.013 Weekend 11.5 7.7 0.302 From first ED to endoscopy 4.32 6.0 14.7 7.7 0.009 Weekday 7.8 8.8 11.5 8.8 0.130 Weekend 7.9 5.4 9.5 8.3 0.178 As noticed in table 12, time to arrival to ED-CHP was significantly higher during the day compared with the night (15h vs. 7h, p=0.003). Patients transferred during daytime had a significantly longer time to endoscopy compared with patients admitted during the night (15h vs. 7h, p=0.009). Patients were predominantly men (67%) with 24% of them with 80 years old or more and similar between groups. The characteristics of the patients are outlined in table 12, according to time and status of admission. Patients' age are not significantly different among the four groups. Patients admitted out-of-hours presented more often with haematemesis (72% and 74% vs. 45% and 56% respectively, p<0.000). Comorbidities were not significantly different among the four groups, but patients admitted to ED-CHP, / Chapter IV - Results 140 during the day, tended to be more often known with metastatic malignancy and vascular disease (p=0.05 and p<0.05). Patients characteristics are detailed in table 13. Total N (%) ED-CHP N (%) 8am-8pm N (%) 8pm-8am Referrals N (%) 8am-8pm N (%) 8pm-8am p Sex Male Female 430 (67) 212 (33) 166 (65) 89 (35) 74 (66) 39 (34) 20 (36) 35 (64) 64 (29) 155 (71) 0.527 Age (years) < 60 >60 - <80 ≥80 214 (33.3) 274 (42.7) 154 (24.0) 73 (28.6) 115 (45.1) 67 (26.3) 32 (28.3) 51 (45.1) 30 (26.5) 23 (41.8) 23 (41.8) 9 (16.4) 86 (39.3) 85 (38.8) 48 (21.9) 0.128 Clinical presentation Hematemesis Melena Hematochezia 374 (58.9) 320 (50.4) 41 (6.5) 116 (45.7) 133 (52.4) 13 (5.1) 73 (74.6) 46 (40.7) 9 (8.0) 31 (56.4) 36 (65.5) 4 (7.3) 154 (72.3) 105 (49.3) 15 (7.0) 0.000 0.021 0.715 Comorbidities (N=638) Cardiac disease Chronic renal disease Blood disorders Chronic liver disease Vascular disease Previous stroke Peptic ulcer disease 84 (32.9) 70 (11.0) 11 (1.7) 78 (12.2) 63 (9.9) 63 (9.9) 84 (13.2) 38 (33,6) 35 (13,7) 3 (1,2) 30 (11,8) 37 (14,5) 27 (10,6) 32 (12,5) 13 (23.6) 15 (13.3) 5 (4.4) 16 (14.2) 12 (10.6) 9 (8.0) 22 (19.5) 38 (33.6) 5 (9.1) 2 (3.6) 10 (18.2) 3 (5.5) 2 (3.6) 3 (5.5) 55 (25.6) 15 (7.0) 1 (0.5) 16 (14.2) 11 (5.1) 25 (11.6) 27 (12.6) 0.185 0.098 0.037 0.383 0.005 0.289 0.074 Table 13: Overall results - Patients characteristics for NVAUGIB and in sub-groups according to time and admission status. / Chapter IV - Results 141 complicated or not Hypertension Diabetes Malignancy Metastatic malignancy Renal or liver Transplanted 291 (45.6) 149 (23.4) 81 (12.7) 20 (3.1) 11 (1.7) 125 (49.0) 68 (26.7) 41 (16.1) 14 (5.5) 8 (3.1) 43 (38.1) 26 (23.0) 16 (14.2) 2 (1.8) 2 (1.8) 27 (49.1) 9 (16.4) 6 (10.9) 1 (1.8) 1 (1.8) 96 (44.7) 46 (21.4) 16 (14.2) 3 (1.4) 0 (0.0) 0.246 0.317 0.084 0.050 0.079 Nº of comorbidities None 1 2 ≥ 3 130 (20.4) 177 (27.7) 154 (24.1) 177 (27.7) 41 (16.1) 63 (24.7) 65 (25.5) 86 (33.7) 25 (22.1) 29 (25.7) 21 (18.6) 38 (33.6) 14 (25.5) 19 (34.5) 10 (18.2) 12 (21.8) 50 (23.3) 66 (30.7) 58 (27.0) 41 (19.1) 0.012 Medication Anticoagulation at presentation Aspirin intake AAS 100 AAS 150 Clopidogrel NSAID use Anticoagulation + Aspirin + clopidogrel Aspirin + Clopidogrel 350 (55.2) 73 (11.4) 95 (15.1) 95 (15.1) 77 (12.2) 129 (20.4) 6 (0.9) 30 (4.7) 139 (54.7) 34 (13.3) 39 (15.4) 35 (13.8) 26 (10.2) 49 (19.3) 4 (1.6) 11 (4.3) 53 (53.1) 11 (9.7) 18 (15.9) 10 (8.8) 18 (15.9) 19 (16.8) 1 (0.9) 8 (7.1) 31 (56.4) 3 (3.6) 5 (9.6) 7 (13.5) 2 (3.7) 15 (28.3) 0 (0.0) 0 (0.0) 120 (56.6) 26 (11.9) 33 (15.6) 25 (11.8) 19 (9.0) 46 (21.7) 1 (0.5) 8 (7.1) 0.342 0.204 0.718 0.591 0.077 0.342 0.538 0.231 PPI before endoscopy N=602 467 (77.6) 186 (75.6) 89 (79.5) 37 (75.5) 155 (79,5) 0.728 Clinical Rockall score 0.150 / Chapter IV - Results 142 Low risk ≤ 2 Moderate risk 3-4 High risk >4 Low risk ≤ 2 Moderate / High risk ≥3 283 (44.7) 254 (40.1) 96 (15.2) 283 (44.7) 350 (55.3) 105 (41.2) 113 (44.3) 37 (14.5) 105 (41.2) 150 (58.8) 50 (44.2) 39 (34.5) 24 (21.2) 50 (44.2) 63 (55.8) 29 (53.7) 16 (29.6) 9 (16.7) 29 (53.7) 25 (46.3) 99 (46.9) 86 (40.8) 26 (12.3) 99 (46.9) 112 (53.1) 0.323 Complete Rockall score (N=627) Low risk ≤ 2 Moderate risk 3-4 High risk >4 71 (11.3) 192 (30.6) 364 (58.1) 35 (13.8) 73 (28.7) 146 (57.5) 7(6.2) 28 (25.0) 77 (68.8) 7 (13.2) 19 (35.8) 27 (50.9) 22 (10.6) 72(34.6) 114 (54.8) 0.115 Low risk ≤ 2 Moderate /High risk ≥3 71 (11.3) 556 (88.7) 35 (13.8) 219 (86.2) 7(6.2) 105 (93.8) 7(13.2) 46(86.8) 22(10.6) 186 (89.4) 0.195 Hemodynamics Stable Heart rate > 100 beats/min Systolic blood pressure < 100mmHg Systolic blood pressure ±SD, mmHg Diastolic blood pressure ±SD, mmHg 350 (56.7) 138 (22.4) 129 (20.9) 120±25 66±14 155 (62.2) 49 (19.7) 45 (18.1) 122±25 67±14 63 (55.8) 21 (18.6) 29 (25.7) 116±24 62±14 31 (57.4) 15 (27.8) 8 (14.9) 125±27 67±15 101 (50.2) 53 (26.4) 47 (23.4) 118±24 65±14 0.103 0.103 0.103 0,024 0.021 / Chapter IV - Results 143 Heart rate ±SD beats/min Hemoglobin ±SD g/dL Hemoglobin ≤ 7 g/dL Hemoglobin > 7 g/dL 92±20 9,0±3,8 175 (27.9) 452 (72.1) 88±19 8,7±2,8 75 (29.5) 179 (70.5) 91±23 9,1±2,7 29 (25.7) 84 (74.3) 94±23 8,7±2,6 22 (42.3) 30 (57.7) 92±20 9,4±5,3 49 (27.9) 159 (76.4) 0.001 0.199 0.047 0.047 EGD was performed in all patients, and 16.8% had to repeat the procedure, because of some limitations, namely blood, food or patient's intolerance, without sedation. The probability of repeating EGD was significantly higher in patients directly admitted to EDCHP. Just 6.8% of the patients were admitted in intensive care units; 15% were discharged and 56% were admitted as inpatients in CHP (figure 10). The first EGD was performed within 24h of presentation in 86% of the patients. Of the 642, 290 (45%) required endoscopic therapy for hemostasis. Peptic ulcer was the main diagnosis (51%) being 52% gastric and 48% duodenal ulcers. Rebleeding was reported in 8.9% and the 30-day mortality in this case cohort was 7.5% (46/615), being the bleeding episode responsible for 30% of the deaths. Significantly more patients endoscoped during 050 100 150 200 250 300 ED-CHP 8am-8pm ED-CHP 8pm-8am Referrals 8am-8pm Referrals 8pm-8am Figure 10: Planning after EGD Discharged Transferred Admitted as in-patients / Chapter IV - Results 144 the night had surgery (p=0.015). The other outcomes were independent of the time or status of admission. Total (%) ED-CHP (%) 8am-8pm (%) 8pm-8am Referrals (%) 8am-8pm (%) 8pm-8am p Rebleeding 8.9 8.3 11.6 6.4 8.7 0.687 Surgery 4.1 1.6 8.0 1.9 5.8 0.015 Inhospital mortality 6 6 6 7 5.1 0.326 30 day mortality 7.5 7.1 8.9 10 6.5 0.774 No adverse events were reported during transfer but during the procedure: one sentinel event (death after cardio respiratory arrest) and four severe (one perforation after therapeutic endoscopy and three aspiration pneumonias); transient tachycardia, hypoxemia or self-limited bleeding were recorded as minor incidents. The median length of hospital stay was 6 days for both admission status groups. Table 14: Overall results - Patients outcomes for NVAUGIB and in sub-groups according to time and admission status. CHAPTER IV RESULTS IVa. Overall Results IVb. Main Results