DSM-IV criteria for generalized anxiety disorder
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6288",leadTitle:null,fullTitle:"Hot Topics in Burn Injuries",title:"Hot Topics in Burn Injuries",subtitle:null,reviewType:"peer-reviewed",abstract:'The aim of this book is to give readers a broad review of burn injuries, which may affect people from birth to death and can lead to high morbidity and mortality. The book consists of four sections and seven chapters. The first section consists of the introductory review chapter, which overviews the burn injuries. The second section includes chapter "Burn Etiology and Pathogenesis," which focuses on burn injuries and clinical findings. The third section consists of chapter "Controlling Inflammation in Burn Injury" and is devoted to the role of inflammatory response, which is fundamental to the healing process, while a prolonged inflammation may lead to scarring and fibrosis. The fourth section consists of four chapters as follows: "Therapeutic Effects of Conservative Treatments on Burn Scars," "Herbal Therapy for Burns and Burn Scars," "Platelet-Rich Plasma in Burn Treatment," and "Surgical Treatment of Burn Scars." The book is easy to read and includes hot topics on burn injury to enhance the reader\'s understanding and knowledge.',isbn:"978-1-78923-131-1",printIsbn:"978-1-78923-130-4",pdfIsbn:"978-1-83881-380-2",doi:"10.5772/intechopen.69253",price:119,priceEur:129,priceUsd:155,slug:"hot-topics-in-burn-injuries",numberOfPages:128,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c13b370b0d6dd78067ad3761613cefdf",bookSignature:"Selda Pelin Kartal and Dilek Bayramgürler",publishedDate:"May 23rd 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6288.jpg",numberOfDownloads:12266,numberOfWosCitations:9,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:30,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:52,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 19th 2017",dateEndSecondStepPublish:"June 9th 2017",dateEndThirdStepPublish:"September 5th 2017",dateEndFourthStepPublish:"December 4th 2017",dateEndFifthStepPublish:"February 2nd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"72686",title:"Prof.",name:"Selda Pelin",middleName:null,surname:"Kartal",slug:"selda-pelin-kartal",fullName:"Selda Pelin Kartal",profilePictureURL:"https://mts.intechopen.com/storage/users/72686/images/5353_n.jpg",biography:"Assoc. Prof. Dr. Selda Pelin Kartal graduated from Hacettepe University School of Medicine. Currently, she is an Associate Professor in the Department of Dermatology at University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital in Ankara, Turkey. She has co-authored over 100 published articles and supervised several master’s and postdoctoral students. Her actual interests are focused on acne, psoriasis, urticaria, autoimmune bullous diseases, Behçet’s disease and cosmetic dermatology.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Ankara University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"189461",title:"Prof.",name:"Dilek",middleName:null,surname:"Bayramgurler",slug:"dilek-bayramgurler",fullName:"Dilek Bayramgurler",profilePictureURL:"https://mts.intechopen.com/storage/users/189461/images/6032_n.jpg",biography:null,institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Kocaeli",institutionURL:null,country:{name:"Turkey"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"177",title:"Emergency Medicine",slug:"emergency-medicine"}],chapters:[{id:"57720",title:"Introductory Chapter: An Introduction to Burn Injuries",doi:"10.5772/intechopen.71973",slug:"introductory-chapter-an-introduction-to-burn-injuries",totalDownloads:1727,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Selda Pelin Kartal, Cemile Tuğba Altunel and Dilek Bayramgurler",downloadPdfUrl:"/chapter/pdf-download/57720",previewPdfUrl:"/chapter/pdf-preview/57720",authors:[{id:"72686",title:"Prof.",name:"Selda Pelin",surname:"Kartal",slug:"selda-pelin-kartal",fullName:"Selda Pelin Kartal"},{id:"189461",title:"Prof.",name:"Dilek",surname:"Bayramgurler",slug:"dilek-bayramgurler",fullName:"Dilek Bayramgurler"},{id:"229047",title:"Dr.",name:"Cemile Tuba",surname:"Altunel",slug:"cemile-tuba-altunel",fullName:"Cemile Tuba Altunel"}],corrections:null},{id:"57336",title:"Burn Etiology and Pathogenesis",doi:"10.5772/intechopen.71379",slug:"burn-etiology-and-pathogenesis",totalDownloads:3245,totalCrossrefCites:6,totalDimensionsCites:6,hasAltmetrics:0,abstract:"As a trauma type, “Burn” is one of the high-frequency accidents in the world. It is mostly caused by electricity, hot water, and chemical agents. A trauma can have acute effects on burns, skin, and other organ systems. These complications might be seen as myocardial infarction, thromboemboli, respiratory, and renal failure. In case of acute burns, the skin surface is severely destroyed. During this period, infection may develop on damaged skin. Therefore, in the treatment of burn wounds, protecting the damaged skin and multidisciplinary approaches are needed for preventing scar formation while healing process.",signatures:"Yesim Akpinar Kara",downloadPdfUrl:"/chapter/pdf-download/57336",previewPdfUrl:"/chapter/pdf-preview/57336",authors:[{id:"213746",title:"M.D.",name:"Yeşim",surname:"Akpınar Kara",slug:"yesim-akpinar-kara",fullName:"Yeşim Akpınar Kara"}],corrections:null},{id:"57431",title:"The Role of the Inflammatory Response in Burn Injury",doi:"10.5772/intechopen.71330",slug:"the-role-of-the-inflammatory-response-in-burn-injury",totalDownloads:2016,totalCrossrefCites:4,totalDimensionsCites:17,hasAltmetrics:1,abstract:"Burns are characterised by significant local swelling and redness around the site of injury, indicative of acute inflammation. Whilst the inflammatory response is fundamental to the healing process, triggering a cascade of cytokines and growth factors to protect against the risk of infection, it is clear that prolonged inflammation can be detrimental and lead to scarring and fibrosis. Severe burns may display chronic, persistent inflammation long after the initial burn injury and may even result in multiple organ failure (MOF) due to systemic inflammatory response syndrome (SIRS). Excessive inflammation in the early stages of healing has been identified as a causative factor in the formation of scars which can be disfiguring, functionally restrictive and may require revisionary surgeries. Therefore, it is imperative that inflammation is effectively managed following burn injuries in order to optimise the benefits it provides whilst actively preventing the complications of inflammation including SIRS, multiple organ failure (MOF) and the development of scarring and fibrosis. Reviewing the current knowledge about the role of the inflammatory response in burns and the treatments available for the management of inflammation during wound healing, highlights the importance of continued research into understanding and developing new approaches to regulate inflammatory responses post-burn injuries.",signatures:"Xanthe L. Strudwick and Allison J. Cowin",downloadPdfUrl:"/chapter/pdf-download/57431",previewPdfUrl:"/chapter/pdf-preview/57431",authors:[{id:"182005",title:"Prof.",name:"Allison",surname:"Cowin",slug:"allison-cowin",fullName:"Allison Cowin"},{id:"222173",title:"Dr.",name:"Xanthe",surname:"Strudwick",slug:"xanthe-strudwick",fullName:"Xanthe Strudwick"}],corrections:null},{id:"57034",title:"The Therapeutic Effects of Conservative Treatments on Burn Scars",doi:"10.5772/intechopen.70833",slug:"the-therapeutic-effects-of-conservative-treatments-on-burn-scars",totalDownloads:1043,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Hypertrophic scar, which can be seen even after minor burn injuries, is a common complication and generally develops within 6–8 weeks following reepithelization. Hypertrophic scar/keloid is often seen when the injury affects the reticular dermis and, in particular, after a deep dermal or full thickness burn. There are various options used in the treatment of burn scar. The purpose of this chapter is to provide the reader a brief information on the conservative treatment methods used in burn scar treatment.",signatures:"Mehmet Unal",downloadPdfUrl:"/chapter/pdf-download/57034",previewPdfUrl:"/chapter/pdf-preview/57034",authors:[{id:"211129",title:"Dr.",name:"Mehmet",surname:"Unal",slug:"mehmet-unal",fullName:"Mehmet Unal"}],corrections:null},{id:"57677",title:"Herbal Therapy for Burns and Burn Scars",doi:"10.5772/intechopen.71665",slug:"herbal-therapy-for-burns-and-burn-scars",totalDownloads:1592,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Burn wound healing is a complex process including inflammation, epithelialization, granulation, neovascularization, and wound contraction. Modern therapies present a large number of options, while traditional therapies are promising effective choices. Plant-based products have been used in the treatment of wounds for centuries worldwide. Recently, the mechanisms behind many of these traditional therapies could be explained in detail. The most commonly found mechanisms behind the herbal source products supporting wound healing are mostly their antioxidant, anti-inflammatory, antimicrobial, cell proliferative, and angiogenic effects. However there is not much more studies demonstrated in patients except Aloe vera and Avena sp., herbal treatment still show a lot of promise in the future. It is important not to ignore possible toxic and allergic effects of plants and phytochemical agents, but the studies mostly resulted with antitoxic effects. Several herbs show efficient results with therapies of wounds also in burn wounds, which may be considered as an option for treatment. On the other hand, herbal treatment in burn wounds still needs to have more clinical and pharmaceutical studies to place in modern therapies safely.",signatures:"Serap Maden, Eemel Çalıkoğlu and Pertevniyal Bodamyalızade",downloadPdfUrl:"/chapter/pdf-download/57677",previewPdfUrl:"/chapter/pdf-preview/57677",authors:[{id:"211350",title:"Dr.",name:"Pertevniyal",surname:"Bodamyalızade",slug:"pertevniyal-bodamyalizade",fullName:"Pertevniyal Bodamyalızade"},{id:"211444",title:"M.D.",name:"Serap",surname:"Maden",slug:"serap-maden",fullName:"Serap Maden"},{id:"211445",title:"Dr.",name:"Emel",surname:"Çalıkoğlu",slug:"emel-calikoglu",fullName:"Emel Çalıkoğlu"}],corrections:null},{id:"57046",title:"Platelet-Rich Plasma in Burn Treatment",doi:"10.5772/intechopen.70835",slug:"platelet-rich-plasma-in-burn-treatment",totalDownloads:1354,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"As a general definition, platelet-rich plasma (PRP) is the concentration of autologous human platelets in a small amount of plasma. PRP contains important growth factors deposited in alpha-granules of platelets and plasma proteins such as fibrin, fibronectin, and vitronectin. PRP has been shown to improve wound healing process in acute trauma wounds, incisional wounds, and chronic nonhealing wounds and is a beneficial agent in reconstructions of soft and hard tissue. Furthermore, PRP enhances differentiation of epithelial cell and collagen bundle organization. Effects of growth factors in PRP on wound healing and successful results obtained with PRP treatment in other types of wound lead to the use of PRP for burn treatment.",signatures:"Mehmet Unal",downloadPdfUrl:"/chapter/pdf-download/57046",previewPdfUrl:"/chapter/pdf-preview/57046",authors:[{id:"212648",title:"Assistant Prof.",name:"Mehmet",surname:"Unal",slug:"mehmet-unal",fullName:"Mehmet Unal"}],corrections:null},{id:"60268",title:"Surgical Treatment of Burn Scars",doi:"10.5772/intechopen.72303",slug:"surgical-treatment-of-burn-scars",totalDownloads:1290,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The relationship between a burns patient and a reconstructive surgeon is normally long lasting and continues lifelong. Patients not only require a surgeon’s professional expertise, but also time, optimism and compassion. Scar management relates to the physical and aesthetic components as well as the psychosocial implications of scarring. Hypertrophic scar formation which can cause debilitating deficiencies and poor aesthetic outcomes might be a result of burn injuries. Although nonsurgical treatment modalities in the early phase of scar maturation are critical to decrease hypertrophic scar formation, surgical management is often indicated to restore function. 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\r\n\r\n\tThe following chapters will offer an overview of the most predominant presentations of Personality disorders in clinical practice, namely the Borderline, Narcissistic, Schizoid and Antisocial types. Case studies arising from clinical practice will be presented and the chapters will offer a comprehensive discussion of the processes and treatment outcomes of various psychotherapeutic models employed in treatment.
\r\n\r\n\tThe final chapter is dedicated to broader manifestations of Personality Disorders and their associated clinical presentations which may have not received sufficient clinical attention, arising challenges and treatment approaches.
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Its lifelong prevalence in the general population is 5% according to the criteria of DSM and 6.5% according to broader criteria of ICD-10.
Among anxiety disorders, GAD patients often consult primary care physicians (PCPs) for their treatment. An international study conducted by the World Health Organization (WHO) found the frequency of GAD in primary health care at 14.9%, 3.7% and 0.9% in Greece, Italy and Turkey respectively. Despite these different figures among countries which are thought to emerge from structural differences of primary health care services, it was found out that the point prevalence of GAD in primary care was much higher (7.9%) than that of the general population. Through reanalysis of WHO\'s data, it was also shown that 25% of these patients have pure GAD without any comorbidity. In light of this data, it can be concluded that GAD is the most frequent mental disorder after depression in primary care, and that patients favour primary health care services for their treatment.
The comorbidity of GAD patients with other psychiatric disorders brings about an increase in the frequency of the health care system use, with longer periods of hospitalization, more frequent use of diagnostic tests and medication, and therefore, a heavy financial burden. This, in turn, implies more serious family problems and prolonged absence from work. There is abundant evidence showing that GAD decreases the quality of life considerably due to invalidity and disability.
It is reported that patients complain of physical symptoms more often than psychological, and worry is cited as the main problem for only 13% of GAD patients in primary care. The patients with GAD mostly consult primary care for aches, sleep problems and somatic problems. Somatic complaints of patients usually appear in the form of chronic medical conditions such as chest pain, chronic fatigue syndrome, irritable bowel syndrome and hypertension, diabetes and cardiac diseases. This is an important factor that complicates the accurate diagnosis of patients and also delays their treatment. The period between the time when the first symptoms of GAD appear and the time of the patient\'s consultation with the family physician or its equivalent can last for up to one year. Furthermore, it can take as long as seven years for the first consultation with the expert at an anxiety clinic. It was observed that about one third of GAD patients were not given a proper psychological diagnosis by family physicians.
Stigmatization is an important factor in insufficient diagnosis and this can account for why a significant number of patients do not express their emotional problems to their physicians. Patients with GAD are often unsuccessful at identifying that their symptoms as related to psychological disorders. People who minimize and normalize their symptoms are mostly young male patients and it is reported that they receive fewer correct diagnoses.
Along all these patient-related factors, it is clear that there are huge discrepancies in physicians’ diagnostic skills, emerging from their knowledge, abilities and approaches. Longer consultation periods do not increase chance of correct diagnosis of diseases either. However, while empathy, interest in psychiatry and asking questions about family and domestic problems can increase the chance for an accurate diagnosis, coexisting organic diseases complicate it further. In a study conducted over a group of patients who mostly rely on using primary care services, GAD was found to be the disease which was most difficult to diagnose and caused most frustration for the physicians. It could be argued that this seriously affects physicians’ skills to diagnose and treat their patients appropriately. It is apparent that physicians require tools to use for diagnosis.
The low rate of recognition and diagnosis of GAD in primary care presents a barrier for appropriate treatment and referrals needed for it. However, primary care physicians are the group with access to the largest body of patients.
The problems encountered in primary care diagnosis and management of anxiety in GAD are multifaceted and multiphase, which complicates the solutions as well. First of all, social interventions, including education campaigns which would improve society\'s approach to mental problems and decrease stigmatization, are required. Furthermore, increasing awareness of primary care physicians and equipping them with proper scanning tools is a necessity. Finally, developing national diagnosis and treatment guidelines, and promoting evidence based medical practice is also of great importance.
Before the 1980s, Generalized Anxiety Disorder (GAD) was labelled as ‘anxiety neurosis’ characterized by excessive worrying and marked symptoms of hypervigilence and anxiety. GAD was first conceptualized in the Diagnostic and Statistical Manuel of Mental Disorders-III (DSM) in 1980 and its diagnostic criteria have changed since then. The current criteria in DSM-IV (Table 1) and the International Classification of Diseases-10 (ICD) (Table 2) for GAD differ considerably with ICD-10 listing a broader spectrum of symptoms. The differences in the understanding GAD between Europe and the United States predominantly based on the fact that ICD-10 is preferred in Europe, while DSM-IV is preferred in the United States (Wittchen & Hoyer, 2001; Lieb et al., 2005). These preferences have a substantial impact on the epidemiological results. The most likely lifetime prevalence for GAD in the general population is 5% (ranges between 0.8-21.7% with different assessment tools in different countries) with DSM criteria and slightly higher, 6.5%, with ICD-10 criteria (Bijl et al., 1998; Wittchen & Hoyer, 2001; Lieb et al., 2005; Mergl et al., 2007; Serrano-Blanco et al., 2010).
A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not and for at least 6 months, about a number of events or activities (such as work or school performance) |
B. The person finds it difficult to control the worry |
C. The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms present for more days than not for the past 6 months). Note: only one item is required in children |
(1) restlessness or feeling keyed up or on edge |
(2) being easily fatigued |
(3) difficulty concentrating or mind going blank |
(4) irritability |
(5) muscle tension |
(6) sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep) |
D. The focus of the anxiety and worry is not confined to features of an Axis I disorder. E.g., the anxiety or worry is not about having a panic attack (as in panic disorder), being embarrassed in public (as in social phobia), being contaminated (as in obsessive compulsive disorder), being away from home or close relatives (as in separation anxiety disorder), gaining weight (as in anorexia nervosa), having multiple physical complaints (as in somatisation disorder), or having serious illness (as in hypochondriasis), and the anxiety and worry do not occur exclusively during posttraumatic stress disorder |
E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. |
F. The disturbance is not due to the direct physiological effects of a substance (e.g, a drug of abuse, a medication) or general medical condition (e.g., hyperthyroidism) and does not occur exclusively during a mood disorder, a psychotic disorder or a pervasive developmental disorder |
DSM-IV criteria for generalized anxiety disorder
Anxiety that is generalized and persistent but not restricted to, or even strongly predominating in, any particular environmental circumstances (i.e. it is "free-floating"). The dominant symptoms are variable but include complaints of persistent nervousness, trembling, muscular tensions, sweating, light-headedness, palpitations, dizziness, and epigastric discomfort. Fears that the patient or a relative will shortly become ill or have an accident are often expressed. |
Anxiety: |
neurosis |
reaction |
state |
Excludes: neurasthenia (F48.0) |
ICD-10 Criteria for Generalized anxiety disorder (F41.1)
The data, both European and non-European, suggests that GAD is most common among older age groups, unlike other anxiety disorders. It also shows that the likelihood of diagnosis of GAD increases with age: for women after the age of 35, and for men after the age of 45. It is relatively rare in the first two decades of life, with lower prevalence rates among adolescents and young adults. However, the age of onset has a bimodal distribution- GAD onset occurs earlier if it is the primary presentation and later if it is secondary (Culpepper, 2002; Lieb et al, 2005). GAD occurs twice as often in women as men, with total lifetime prevalence rates of 6.6% and 3.6%, respectively (Carter et al., 2001; Allgulander, 2006). Other factors significantly associated with GAD are determined to be: discontinued marriage (separated, widowed, or divorced), unemployed or being a house-wife while urbanicity, low income, fewer years of education, more life difficulties, and chronic medical disorders and religion showed limited associations (Wittchen & Hoyer, 2001; Young et al., 2001)
Similarly to patients that suffer of panic disorders, GAD patients often consult primary care physicians for their treatment. An international study conducted by the World Health Organization (WHO) found the frequency of GAD in primary health care at 14.9%, 3.7% and 0.9% in Greece, Italy and Turkey respectively. Despite these different figures among countries which are thought to emerge from structural differences in primary health care services, it was found out that the point prevalence of GAD in primary care was much higher (7.9%) than that of the general population (Ustun & Sartorius, 1995). Through reanalysis of WHO\'s data, it was also shown that 25% of these patients have pure GAD without any comorbidity (Lieb et al., 2005). The GADIS study determined the prevalence of pure GAD at 4.1%, and all GAD at 8.3% in primary care, while Kroenke et al. found the prevalence of GAD in primary care to be 7.6% (Ansseau et al., 2005; Kroenke et al., 2007). In light of this data, it can be concluded that GAD is the most frequent mental disorder after depression in primary care, and that patients favour primary health care services for their treatment.
GAD symptoms wax and wane over time, with exacerbations of acute anxiety to response stress. Many patients with GAD readily report “I’ve been a worrier all my life”. Studies support its episodic pattern with remission and recurrence periods evident for many years. (Wittchen & Hoyer, 2001; Allgulander, 2006).
GAD is a disabling condition and a social disability as severe as chronic somatic disorders such as arthritis, hypertension, asthma, and diabetes (Maier et al., 2000; Wittchen & Hoyer, 2001; Kessler et al., 2001; Roy-Byrne Wagner, 2004 ; Lieb, 2005). Wittchen et al. have shown that only 13% of GAD patients in primary care identify anxiety as the primary problem (Wittchen, 2002). Mostly, patients complain of somatic and sleeping problems (Wittchen & Hoyer, 2001). Accompanying symptoms include muscle tension, headache, muscle aches, restlessness, irritability, gastrointestinal symptoms, and difficulty in concentrating, fatigue, insomnia (Shearer, 2007). Patients are unlikely to directly and openly complain of anxiety symptoms. Cardiac and gastrointestinal symptoms of anxiety deserve special attention so as not to be misinterpreted in differential diagnosis and to avoid high costs of potential unnecessary screening for accurate diagnosis. GAD was determined to be primary diagnosis among 20% of patients with an atypical chest pain; 55% of patients with chest pain & normal coronary arteries; and 50% of patients seeking a cardiac evaluation (Roy-Byrne Wagner, 2004). Similarly, - in patients with inflammatory bowel syndrome GAD was showed to be in high prevalence (Roy-Byrne Wagner, 2004). A longitudinal study that determines the under-recognition of mental disorders showed that 18% of patients that had severe symptoms of depression or anxiety according to the general health questionnaire had never received a diagnosis from their general practitioners (GPs) (Kessler et al., 2002).
In another study, first three common reasons for the GP visit were listed as oto-rhino-laryngology (ORL), cardiovascular, and rheumatologic problems. However, a psychiatric problem was mentioned only in 5.4% of the cases. On the other hand, for the same sample, the prevalence of a psychiatric disorder was found 42.5%, and GAD prevalence was 10.3%, detected by PRIME-MD (Ansseau et al., 2004). A different study showed that 69.6% of the patients reporting anxiety/depression as a reason for consulting their GP had GAD (Ansseau et al., 2005).
Not only patients and primary care physicians’ factors, but also the waxing and waning nature of GAD, leading to a “
Chronic nature of GAD with remissions and recurrences, symptoms do not meet the criteria in periods of recovery between episodes and substantial overlap with other medical and psychological disorders may make it difficult to easily detect it (Kroenke et al., 1997, Roy-Byrne Wagner, 2004; Allgulander, 2006). Major depressive disorder is seen in at least one-third of primary care patients with GAD (Carter et al., 2001; Stein, 2003). Comorbidity with panic disorder, social phobia and specific phobia, and post-traumatic stress disorder is also common. Comorbidity is generally associated with increased severity and persistence of the disorders (Allgulander, 2006). However, GAD patients were found to be diagnosed with two or more comorbid disorders more often than any other disorder (Carter et al., 2001). Rodrigues et al. showed that primary care patients in the study population showed as much Axis I comorbidity as psychiatric treatment-seeking population. This is an important finding that questions previous assumptions about treatment-seeking in mental health settings as an indication of illness severity (Rodrigues et al.; 2004).
It is known that there is a wide variation in the ability of primary care physicians to diagnose GAD due to differences in knowledge, skills, and attitudes. Not only factual knowledge but also clinical skills, particularly communication skills and interview techniques, are important in the management of psychiatric disorder. Other obstacles have been mentioned: competing demands on PCPs time to interview patients within the limit of typical 15-min clinical encounters, frequent somatisation of mental disorders, underlying comorbidity, and preoccupation of an organic disease. However, empathy, an interest in psychiatry and asking about family and problems at home can help with the recognition (Ansseau et al., 2004; Rollman et al., 2005; Allgulander, 2006; Tylee & Walters, 2007). Harman et al. reported that vast majority of PCPs’ diagnosis were branded “anxiety, unspecified”. They concluded that this may reflect that the symptoms of primary care patients do not fulfil a specific diagnosis like GAD, or current description of anxiety disorders in commonly used classifications is too complicated to be easily applied by PCPs (Harman et al., 2002).
With regards to the patients, this discrepancy can be due to the considerable resistance to a psychiatric diagnosis and reluctance to discuss their psychiatric condition for the fear of stigmatization, and may account for 45% of people failing to share their emotional problems with their physicians (Cape & McCullech, 1999; Tylee & Walters, 2007). Another factor is that patients do not consider their psychiatric symptomatology as sufficiently unusual or troublesome to be mentioned until the underlying anxiety is identified (Harman et al., 2002; Ansseau et al., 2004). Kessler et al. found different styles of symptom attribution, and showed that patients who attribute a psychological cause are more likely to be recognized when compared to patients who normalize or minimize their symptoms. Normalisers were determined as younger and male patients (Kessler et al., 1999). Harman et al. argued that reimbursement issues or concerns over a patient’s willingness to be diagnosed with an anxiety disorder could also be possible explanations (Harman et al., 2002). Besides these, a qualitative study had shown that patients were open to suggestions from their GPs or otherwise. Furthermore, several described their GPs as “marvellous” or “has never let me down”. They believed it was helpful to talk to someone about their problem; however the search for this person was seen as difficult. Patients expressed the need for an easier access to professional help, suggesting their GPs should be more active in referrals, checking up on the patients’ progress through phone calls, follow-up sessions, and home visits. Patients also expressed concern about interfering their GP’s busy schedule, because of GP’s involvement with more pressing medical cases. However some also conserve their hope for their GPs to do more than prescribe drugs, waiting for encouragement of to disclose their emotional or psychological problems. Another concern of theirs was the waiting time, since they wish to speak to someone at the moment they are feeling bad, instead of waiting for appointments (Kadam et al., 2001).
Since GAD is highly prevalent in the primary care setting, patients with the disorder are likely to be high users of primary care health services, both in terms of the frequency of visits and the sheer number of patients contacting primary care providers because of problems associated with the disorder (Wittchen & Hoyer, 2001). Young et al. showed that during a 1-year period, 84.3% of individuals with an anxiety disorder only visit PCPs (Young et al., 2001). Harman et al. found the proportion of visits to PCPs as 46.5-48.2%, which still holds true today. They also reported that anxiety disorder diagnose were recorded more often during visits where the physician had seen the patient before, and a depression diagnosis had also been recorded during that same visit (Harman et al., 2002). Patients with pure GAD are 1.6 times more likely to have four or more visits to PCPs than patients without GAD or major depressive episodes (MDE) (Wittchen, 2002). Bélanger et al. determined that patients with positive screening for GAD reported more annual medical visits (5.3 versus 3.4) than other patients, and 44.5% of the positive screening group reported consulting a family physician five times or more yearly, compared with 20.0% in the negative screening group. However, they did not report consulting other resources more often, suggesting that patients with GAD might mostly seek treatment from PCPs (Bélanger et al., 2005). Kronke et al. determined the self-reported 2.9 (2.2-3.6) physician visits in the preceding 3 months (Kroenke et al., 2007).
GAD patients have to be identified so they can be properly treated. Wagner et al. found that family physicians (FPs) diagnosed 39% of cases correctly while 29.3% left with no psychological diagnosis (Wagner et al., 2006).
There is an obvious need for tools that will help PCPs in diagnosing and monitoring GAD patients. There are several recommended specifically for GAD, such as Generalized Anxiety Disorder Inventory (GADI), GAD-7; tools for severity assessment such as Hamilton Anxiety Scale (HAM-A); and tools for measurement of functional impairment due to anxiety such as Overall Anxiety Severity and Impairment Scale (OASIS). Web-based screening can also be a choice as being cost-efficient (Allgulander, 2009; Katzman, 2009; Roy-Byrne, 2009). Ruiz et al. showed that GAD-7 highly correlated not only with specific anxiety measures but also with disability measures, which can be used for exploring the level of disability in GAD patients in primary care setting (Ruiz et al., 2011).
In the absence of systematic screening, 30-40% of anxiety and depression patients are identified in primary care setting. There are studies showing evidence for and against the screening. Some reviews point that screening alone does not improve patient’s outcome. However, others concluded that screening has increased benefits when combined with effective treatment and follow up. A barrier for screening is that tools’ length, specificity for a single disorder or both. Means-Christensen et al. recommended Anxiety and Depression Detector (ADD) as screening instrument for anxiety and depressive disorders in primary care. ADD’s sensitivity and specificity ranges between 0.87-1.0 and 0.42-0.68, respectively (Means-Christensen et al.; 2001). Rollman et al. suggested that PRIME-MD can be used in identifying primary care patients with GAD as a part of broader strategy to improve quality of care for GAD patients (Rollman et al., 2005).
PCPs have to use their advantage of continuous contact and communication skills for efficient history taking. To aid accurate diagnosis and to rule out other possible diagnosis, both the patient’s and the family’s histories should be assessed carefully. Recent life events and other health problems including depression, substance or alcohol abuse and dependence should be noted. Multiple visits to PCPs, consultations with different specialists such as gastroenterologists, and consultations that end with no definite diagnosis should be carefully considered (Katzman, 2009).
There is abundant evidence not only on the impairment and disability but also the reduced quality of life in GAD patients. Hospitalization and loss of productivity were the two major components of costs both in patients with and without comorbidity. Health care utilization rates were higher among those with comorbid GAD patients compared to pure GAD (Lieb et al., 2005).
The burden of disability is clearly greater as the number of comorbidities increases (Wittchen et al., 2002; Kroenke et al., 2007; Löwe et al., 2008). Majority of pure GAD patients (66.7%) report impairment of occupational functioning, and selfreported disability days were 9.9 days in the preceding month. This was reported as 15.3 days for patients with pure MDE, and 16.5 days for comorbid GAD and MDE (Witthchen et al., 2002). Kroenke et al. reported in their study that self-reported disability days of the patients with pure GAD during the previous 3 months were 18.1 days (Kroenke et al., 2007). A recent study comparing the functional impact of different anxiety disorders and their combinations showed that disability in GAD was significantly less present in comparison with other anxiety disorders. However, all measures of functioning and disability, except for physical functioning, showed substantial impairment in the overall sample when compared to general population. (Sherborne et al., 2010). ESEMed study found that GAD is associated with substantial level of disability as well as a decrease in the quality of life (Alonso et al., 2004). Revicki et al. showed that anxiety symptoms of GAD patients in primary care settings were associated with impairments in generic health status, disability, disease-specific quality of life, and preference-based measures of health-related quality of life (Revicki et al., 2008). In the WHO Primary Care study, 27% of the patients with GAD reported moderate or severe social disability, with a mean loss of 4.6 work days due to disability in the month preceding the assessment. When GAD was accompanied by major depression, the mean number of lost work days increased to 8.0 days (Lieb et al., 2005).
Presence of GAD, especially comorbidity with major depression, leads substantial impairment of social, professional, and family conditions rated by Sheehan disability scale (Wittchen & Hoyer, 2001; Ansseau et al., 2005; Olfson and Gameroff, 2007). The most serious effects of GAD were observed in the subscales for emotional role limitations and physical health role limitations (Stein, 2003). In a study where Medical Outcomes Study Short Form-20 was used to determine functioning in GAD patients, all six domains of the scale were determined as impaired (Kroenke et al., 2007).
Andlin-Sobocki and Wittchen reported total direct medical costs at €1958 and €3194 and indirect costs at €969 and €1659 for GAD and GAD with comorbidity, respectively (Andlin-Sobocki and Wittchen, 2002). Olfson and Gameroff found that patients with GAD had a significantly higher median medical cost than patients without GAD ($2775 versus $1448), and patients with GAD and high pain interference had the highest mean predicted medical cost, $42.620. They also showed that GAD patients had a greater likelihood of making an emergency department visit (Olfson and Gameroff, 2007).
The proper management of GAD in the primary care settings should not include only pharmacotherapy or psychotherapy but also education of patients and their families, counselling for lifestyle changes, as well as beneficial, continuous support, insomnia management, and development of coping strategies to manage their worries (Culpepper, 2002). There is no evidence-based approach for the combination of different treatment options for GAD patients so there is a need for further researches including large study populations targeted on current practice (Allgulander, 2009).
Education about GAD for both patients and their families must include its waxing and waning nature that can be managed by therapeutic interventions, compliance monitoring and feedback, and it should not reflect either moral weakness or character flaws leading to stigmatisation issue. Counseling; lifestyle changes like exercise, decreasing alcohol, caffeine, and tobacco consumption; regulating sleep; and controlling external stimuli for sleep improvement are encouraged. As insomnia, acute or chronic, is a norm among patients, PCPs have to understand and monitor its severity. Questions about “sleep hygiene”, use of alcohol, daytime sleepiness and problems in functioning can be helpful. Although patients often require short-term pharmacological therapy for their insomnia at the time of initial diagnosis (especially if insomnia is the presenting symptom), or at times of acute exacerbations, the priority of the physician should be helping patients to develop appropriate lifestyle changes that will promote its long-term control. GAD patients often find themselves rehashing problems and unmet expectations, especially during exacerbations, which they find hard to cope with. Simple anxiety coping techniques that help in gaining improved sense of self-control in times of crises can be taught (Culpepper, 2002;Allgulander, 2009; Davidson et al., 2010).
GAD patients deserve effective medical treatment with short and long-term goals. The short-term goals of treatment include reduction in somatic and psychic symptoms, and resolution of insomnia. Long-term goals should include achieving fully functional status that is affected by anxiety, preventing relapses or recurrences, and treatment of comorbid disorders GAD patients suffer from, such as depression. PCPs need to be aware of short and long-term adverse effects of their treatment like worsening of insomnia and agitation, and weight gain and sexual dysfunction, respectively (Culpepper, 2002).
Pharmacotherapy is the most common treatment option chosen by the physicians that needs to be emphasized as an extended treatment option. There are several treatment guidelines and a general consensus among these guidelines is that the first-line pharmacotherapy for GAD patients should include selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) (Katzman, 2009). The SSRIs such as paroxetine, first licensed SSRI for GAD, escitalopram; SNRIs such as venlafaxine, and duloxetine (recently approved in United States for GAD treatment), buspirone, and benzodiazepins are commonly used agents in primary care (Katzman, 2009; Davidson et al., 2010). Tricyclic antidepressants and monoamine oxidase inhibitors should be reserved for patients not responding other regimens as they have potential for lethal overdose and serious adverse effects. Benzodiazepines are generally recommended for short-term use as they provide immediate relief of insomnia and somatic symptoms; however, those have less effect on psychological symptoms. Their long-term use causes problems of addiction and withdrawal leading conflicts with PCPs. Benzodiazepine use is also problematic for elderly due to the side effects like falling, memory impairment, and loss of coordination, drowsiness and confusion. PCPs have to be aware of adverse effects of these substances when used with other drugs like hypnotics, sedating antidepressants, opiate analgesics, anticonvulsants, anti histamines, and alcohol. (Culpepper, 2002; Davidson et al., 2010). Buspirone has disadvantages of delayed onset effect, short half-life, failure to treat comorbid anxiety or depressive disorders, and is generally less effective than the benzodiazepines, so it is not recommended as first-line treatment for GAD. Hydroxyzine, an antihistaminic, was also reported to be effective for GAD. Due to its sedating and anticholinergic effects, slow onset of action, and lack of efficacy for its comorbids, it is not preferred as first-line treatment (Davidson et al., 2010). SSRIs and an SNRI, venlafaxine are all equally efficient for treating GAD. When choosing between them, some parameters that need to be considered are cost and generic availability, the risk of breakthrough symptoms when a dose is missed, the ease of titration, the potential interaction with other drugs, and adverse effects. Venlafaxine, the first approved drug for GAD, is a valuable first-line treatment option for PCPs, indicated for long treatment of GAD, and also effective in comorbid depressive symptoms and depression. Its dosage should be titrated to minimise its adverse effects, such as nausea, dizziness, dry month, sleepiness. Patients should be monitored for a significant increase in blood pressure. Adverse effects include orthostatic hypotension, sweating, and urinary hesitancy (Culpepper, 2002; Davidson et al., 2010). Paroxetine has the disadvantages of long-term weight gain, and withdrawal symptoms in case of dose omission. Evidence is emerging for atypical antipsychotics that they are effective in the treatment of patients with anxiety disorders both as monotherapy and augmentation to the standard treatment (Katzman, 2009; Davidson et al., 2010).
There are different psychotherapy approaches and the most commonly used one is Cognitive-Behavioural Therapy (CBT). CBT includes psychoeducation, symptom management techniques, cognitive restructuring, exposure to anxiety producing events, relaxation training, and self-monitoring as important first-line treatment options in GAD with the advantage of patient preference and lack of adverse effects (Katzman, 2009). Although it was demonstrated that CBT is the most effective psychological treatment for GAD, clinical response for the treatment was found at less than 50% (Davidson et al., 2010). It is difficult to deliver the treatment adequately, as it needs extensive training of the therapist and time to take effect (van Boeijen et al., 2005). Although it is not possible for PCPs to provide CBT to their GAD patients they should act as guides in selection of experienced CBT therapists, prescribe and monitor pharmacotherapy in coordination with the patient’s therapist, and help patients to use the therapeutic approaches of CBT following the conclusion of formal therapy, especially when they meet new stressors. Attempts have been made for CBT modifications such as ‘self-help’ approaches including ‘bibliotherapy’ (written format, self-help manuals), communication with peers, computerised systems, using a telephone and interactive voice response (Bower et al., 2001; van Boeijen et al., 2005a, Allgulander, 2009). Bower et al. provided some preliminary evidence about self-help packages may offer some clinical advantages over routine primary care for anxiety and depressive disorders and van Boeijen et al. concluded that with more time spent on guidance on the use of the self-help manual, positive results can be achieved for even the patients with longstanding anxiety symptoms (Bower et al., 2001; van Boeijen et al., 2005a). It was shown in the study that the primary care patients with GAD may be treated by their GPs as effectively as after their referral to a psychiatric outpatient clinic, and self-help manual usage is easier for GPs than less structured guidelines resulting in fewer referrals to specialized care (van Boeijen et al., 2005b). Principles of CBT can also be useful while counselling with “high utilisers” and patients suffering acute exacerbations. PCPs can help patients identify and correct their misconceptions about events they perceive as worrying and automatic thought processes that underline the misconceptions, and to develop self-regulation of these thoughts, feelings, and behaviours, namely cognitive restructuring (Culpepper, 2002). Another form of promising psychotherapy for GAD patients is the “well-being therapy” (Davidson et al., 2010).
A recent study published recommended a “unified approach” to the diagnosis, care management, and pharmacotherapy of primary care anxiety addressing the difficulty of assessing and managing multiple anxiety disorders in the primary care setting. The method emphasizes the identification of other medical or psychiatric comorbidities that can complicate the treatment, an approach for the initial education of the patient and discussion about treatment based on motivational interviewing, valid monitoring, an algorithmic approach for the selection of initial pharmacotherapy, and selection of alternative or adjunctive treatments (Roy-Byrne et al., 2009). This approach as a part of flexible treatment-delivery model, namely CALM (“Coordinated Anxiety Learning and Management”), was studied as a randomised controlled trial and compared with usual care in primary care settings. Roy-Byrne concluded that for patients with anxiety disorders treated by PCPs, a collaborative care resulted in greater improvement in managing anxiety symptoms and functional disability, and increasing quality of care over 18 months (Roy-Byrne et al., 2010).
Young et al., defining poor-quality care as no care or inappropriate care in their study, showed that 80.5% of individuals visiting only PCPs had a poor-quality of care. Patients receiving poor-quality care from PCPs were less likely to report evaluation of mental health, recommendation of psychiatric medication, or referral to a mental health specialist. Patients not receiving appropriate care were most often most often from the following groups: men, black, older adults, young adults, people with only primary or no education, and people of lower socioeconomic status (Young et al., 2001). Stein et al. found that the level of appropriate care for anxiety disorders was moderate to low in patients that attended a university affiliated primary care practice. Nearly one third of the patients had received counselling from their PCPs, with less than 10% receiving help from a mental health professional, including multiple elements of CBT. Approximately 40% of patients underwent appropriate pharmacotherapy in the preceding three months. However, only 25% received it at a minimally adequate dose and duration. Different studies determined different factors that had effects on receiving appropriate treatment. In one, the patients with comorbid depression and/or medical illnesses were more likely to receive appropriate treatment, while patients from ethnic minorities were less likely (Stein et al., 2004). Hyde et al., found that with greater severity of disease, measured by total score of GHQ-12, male patients had a significantly increased probability of receiving active treatment (Hyde et al, 2005). Weisberg et al. also emphasised in their study that racial/ethnic minority groups were less likely to be receiving treatments from psychiatrists (Weisberg et al., 2007).
Young et al. discussed that there are many factors that can contribute to improper care and management of depressive and anxiety disorders. These include the perceived need, willingness for care, insurance coverage, and detection by physicians, and knowledge and beliefs of health care providers regarding effective treatment (Young et al., 2001). In a study carried out with a subsample of ESEMeD, the percentage of patients receiving adequate treatment in specialised and general medical care were 31.8% and 30.5%, respectively. In this study factors associated with appropriate treatment were living in a large city, a high education level, and a good self-rated health state (Fernándes et al., 2006). Weisberg et al. pointed out that primary care patient who were not receiving pharmacotherapy for their anxiety disorder claimed two main reasons for this. One was that their doctor never recommended treatment and the other was that they did not believe in medication for emotional problems. In the same study the most commonly claimed reasons for not receiving psychotherapy were patients’ lack of belief in psychotherapy, and their ignorance about the treatability of their emotional problems. Other barriers frequently mentioned for psychotherapy, but rarely for pharmacotherapy were cost, convenience, not knowing how to get into therapy (Weisberg et al., 2007). All of these seem to have a common base with barriers for accurate diagnosis.
In a study searching for the cause and length of delays in care of specific subcategories of anxiety disorders, it was found that GAD patients seek help from their family physician or his/her equivalent 10.3 months after showing symptoms and visit an anxiety clinic for 83.8 months after showing symptoms (Wagnet et al., 2006).
It is obvious that problems encountered in diagnosis and management of GAD in PHC is multifaceted and multiphase and there is a need of integration of mental health in primary care. Primary care has the potential to reach the whole community as being the first point of contact and patient-centred interaction depending on long-lasting, trust based communication. This is also a support for the continuity of care, which is especially important for GAD patients having relapses and remissions. These advantages of primary care, along with all its handicaps can facilitate an integrated treatment approach (Rakel, 2007).
In a systematic review evaluating the effectiveness of interventions aimed to improve recognition, diagnosis and management of patients with anxiety disorders, it was concluded that the most promising choice of care in general practice is a combination of professional interventions with organisational interventions, including an education component where an external expert such as a nurse therapist or a psychologist is introduced (Heideman et al., 2005).
A report prepared by WHO and WONCA (World Organization of Family Doctors) put forward the principles for the integration of mental health into primary care that are, naturally, appropriate for GAD. Some of these principles are supported in this paper, especially for GAD. These include: adequate training of primary care workers, limited and doable tasks for mental care, support to primary care by specialist mental health professionals and facilities, access to essential psychotropic medications in primary care, and collaboration of PCPs with other government non-health sectors, nongovernmental organizations (WHO & WONCA, 2008).
GAD is the most prevalent anxiety disorder in primary care. Its comorbidity is well-documented, leading higher economic burden and a decrease in quality of life. Primary care settings are the best way of ensuring that GAD patients can get the care they need as they are accessible, affordable, acceptable, and cost-effective. Barriers for diagnosis and management of GAD in primary care include: nature of disease, patient- and physician-related factors, and societal factors such as stigmatisation. The proper management of GAD is also multifaceted, and multistage, which means that PCPs needs appropriate counselling with guidelines and screening tools. Primary care is the place that can ensure patients achieve care in a holistic manner, addressing both their physical and mental health needs. Advantages of primary care have to be taken into account for quality improvement programs that will be implemented to enhance awareness and utilization of appropriate treatment options.
Researches accurately reflecting, and modelling the complexities of recognition in primary care
Models that increase patients’ and society’s awareness and physicians’ recognition of GAD
Effect of patients’ attribution styles on the physician’s recognition and recommendations needed to be studied for solutions to cope with the situation and achieving a more accurate diagnosis
Development of reliable and easy to use screening tools/instruments, and increased frequency of their use in primary care setting
Professional and organisational interventions for improvement of diagnosis and treatment of GAD need to be studied with a long-term follow up
Evidence to support the therapeutic value of combined treatments for more complex cases
Data showing the degree of unmet needs for treatment of GAD patients with economic burden, due to inappropriate treatment and inadequate inpatient and outpatient interventions
Studies that provide a chance to understand the reasons underlying low rates of quality care, and implementation of measures to improve them.
Infection, preterm birth, and perinatal complications including asphyxia are among the leading causes of neonatal deaths worldwide [1, 2]. Neonatal and antenatal mortality and morbidity is most often associated with preterm birth that can result in respiratory complications, developmental abnormalities, and high-risk of infections [3, 4]. Infection has been reported in approximately 23% of worldwide neonatal deaths with an estimated 84% of instances being preventable with proper medical treatment [1, 5]. Preterm birth results in the majority of neonatal morbidity and mortality, is the direct cause of approximately 35% of neonatal deaths worldwide, and is the major risk factor for all types of neonatal deaths [1, 3, 4, 6]. Hypoxic birth asphyxia is expected to cause approximately 30% of worldwide neonatal mortality, identified by the inability to perform voluntary breathing at birth, can be observed intrapartum with techniques including Doppler ultrasound and auscultation, and can be diagnosed by an arterial pH in the umbilical cord less than 7.2 [7].
Some of the most common birth defects include congenital heart disease (CHD), down syndrome, and neural tube defects. Congenital cardiac complications are the most common form of congenital abnormalities, with an estimated worldwide prevalence in about 0.8% of all live births, resulting in approximately 1/3 of all congenital abnormalities that cause significant medical and social consequences [8, 9]. Down syndrome is expected in about 1 in 400–1500 births, is the most common chromosomal abnormality, can be diagnosed early in pregnancy with chorionic villus sampling or amniocenteses, and predominately results from trisomy of chromosome 21 [10]. Global neural tube defect prevalence is estimated at 0.05–1% of live births, are characterized by improper closure of the neural tube during fetal development, are commonly asymptomatic, with spina bifida being the most common type, of which the most severe is myelomeningocele [11, 12, 13].
The understanding of normal
MRI sequence for fetal brain analysis include functional imaging, structural imaging, and diffusion imaging [25]. The predominant sequences used in fetal MRI are single-shot T2W (SST2W) sequences, such as rapid acquisition with relaxation enhancement (RARE) sequences on Bruker, Single-Shot half-Fourier Turbo Spin Echo (SShTSE) on Philips, Single-shot Fast Spin Echo (SSFSE) on General Electric, and half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences on Siemens, with protocols provided by the MRI vendor [22, 26]. These T2W sequences are quick enough to be acquired without sedation and are common for neuroanatomical fetal imaging; [9] with other common sequences being T1W to view hemorrhaging, perfusion MRI, diffusion MRI, and spectroscopy [9, 22]. Default SST2W sequences are generally capable of good image generation with 1x1x4 mm voxel size; using half-Fourier acquisitions, with refocusing pulses with flip angles between 120°-150° [22]. Though difficult to implement, diffusion-weighted imaging (DWI) allows identification of ischemic brain lesions, while T1W images can provide improvement over T2W for detection of calcifications, fat, and hemorrhaging [26].
Fetal cardiac sequences are often balanced steady state free precession (bSSFP) and HASTE to encompass small voxel size and reduce acquisition times needed to avoid motion artifacts, with bSSFP being particularly beneficial for imaging blood vessels and cavities containing fluid [26, 27]. Fetal cardiac MRI can be used to view structure, function, vasculature; in addition to performing quantitative MRI measurements including blood flow velocity and oxygen saturation [27]. Blood oxygen level-dependent (BOLD) functional MRI sequences have shown useful for illustrating the improvement of fetal oxygenation during maternal respiratory oxygen therapy for fetuses with impaired cerebral oxygenation resulting from certain types of CHD [28]. Abnormal placenta pathology has been linked with high rates of CHD and is a possible compounding factor for higher severity brain lesions [29]. Neurological implications are not distinct from CHD. Impaired cardiac development is linked with mild brain injury, delayed maturation, shorter gestational age, and smaller brain volumes [30, 31]. Fetal cardiac MRI complications include the smaller size of the fetal heart, lack of gating technologies, and higher heart rate [27].
The primary safety concerns in fetal MRI involve radiofrequency exposure in terms of specific absorption rate (SAR), high acoustic noise, and possibility of peripheral nerve stimulation [22]. MRI is generally considered safe during pregnancy with no evidence of harming the fetus, but is typically not recommended when the fetus is less than about 13 weeks gestational age, and gives best information after completion of organogenesis [22]. The United States Food and Drug Administration (FDA) fetal MRI SAR limit is set at 4 W.kg−1 [22, 32]. Fetal MRI scans are usually recommended to be performed at 1.5 T, and as a “golden rule”, remain below 25 seconds [20, 22]. 3 T fetal MRI is often used only within research settings because the SAR is four times higher than at 1.5 T; with the upper limit generally at 4 T for research applications [9]. Although, some institutions perform routine 3 T fetal imaging during the late second trimester and throughout the third trimester [33]. Contrast enhancement is not recommended in fetal MRI, thought to enter into the fetal vasculature, passing through the renal system, before emptying into the amniotic fluid [9, 34].
Prenatal MRI is most routine for neural abnormalities because of the improved capability for fetal brain scans. In addition to treatment planning of delivery complications, a variety of conditions have high diagnostic rates with fetal MRI, including diagnosis for mild to moderate ventriculomegaly, a variety of neural tube defects, posterior fossa malformations, and twin-to-twin transfusion syndrome [9, 35]. A USA retrospective study for fetal neurology consultations (n = 94) with diagnostic MRI over 14 months reported the most common conditions were posterior fossa malformations, agenesis or dysgenesis of the corpus callosum, congenital acqueductal stenosis, ventriculomegaly, isolated malformations of cortical development, and holoprosencephaly at 19%, 15%, 14%, 11%, 8.5%, and 6%, respectively [36].
Malformations of cortical development are a collection of developmental malformations resulting from disruption during one of the stages of cerebral cortex formation, often causing cognitive impairment, cerebral palsy, and epilepsy. The cortical development occurs in three major stages, including neuronal stem cell proliferation, neuronal migration along radial glial fibers or axons to the developing cerebral cortex, and neuronal organization [37]. Malformations due to abnormal neuronal stem cell proliferation include microcephaly, megalencephaly, and cortical dysplasia. Malformations during neuronal migration and failure for proper cessation of neuronal migration, include: periventricular heterotopia, subcortical band heterotopia, classic lissencephaly, and cobblestone lissencephaly. While, neuronal organization abnormalities include polymicrogyria and schizencephaly [37, 38]. Historically, autopsy or surgical tissue samples were used for diagnosis of these conditions, being difficult to diagnose with ultrasound. MRI has greatly improved the ability to diagnose these conditions during development, rather than in childhood [39]. Retrospective assessment of cortical development malformations has shown high diagnostic accuracy of fetal MRI when compared to postnatal MRI [40].
Ventrigulomegaly is characterized by dilation of the cerebral lateral ventricles during fetal development. Congenital hydrocephalus is a type of ventrigulomegaly that results specifically from increased cerebrospinal fluid pressure, which causes birth defects resulting in abnormally large head size and many other anomalies, and most frequently results from aqueductal stenosis from outlet obstruction in the third ventricle [41, 42]. An illustration of hydrocephalus is shown in Figure 1. Characteristic findings seen postnatally are not often observed prenatally, such as aqueduct funneling or obstruction. Fetal MRI diagnostic indicators, for disease severity from aqueductal stenosis, include the extent of enlargement in the lateral and third ventricle, increased size of the third ventricle of inferior recesses, and observance of diverticulum outpouching in the lateral ventricles [43]. A cohort at the national maternity hospital in the Republic of Ireland reported suspected ventriculomegaly as the most common indication for fetal MRI at the facility, with severe ventriculomegaly (exluding termination) showing a 72% survival rate (n = 74) and a 65% rate for cesarean delivery (n = 72) [44].
Illustration of hydrocephalus with MRI. Rumruay/
Failure of neural tube closure during development results in a variety of neural tube defects, causing spinal anomalies in cases of spinal dysraphism like spina bifida; or cranial anomalies like with anencephaly, characterized by absence of a major portion of the cranium. Though, anencephaly is less indicated for MRI [45]. Distinguishing characteristics of common types of spina bifida are shown in Figure 2. Worldwide incidence varies geographically, but estimated on average about 0.1–1% of live births, with anticonvulsants correlating with increased risk, and folic acid associated with reduced risk of neural tube defects [45]. Spinal dysraphism occurs from improper closure of the spinal cord and surrounding membranes during fetal development, and can be classified by open or closed. Closed spina bifida accounts for about 15% of instances, with spina bifida occulta as the most common form, and is usually asymptomatic [33]. Open spina bifida accounts for about 85% of open spinal dysraphisms with myelomenengocele (MMC) and myelocele being predominant, and nearly always presents with Chiari type II malformation [33]. The randomized MOMS trial compared spina bifida outcomes from fetal surgery compared to surgery after delivery, with fetal MRI playing a pivotal role in treatment planning. Outcomes showed fetal surgery for MMC allowed less need for cerebrospinal fluid shunt placement, improved cognitive function in early childhood, though higher risk of preterm birth was observed in the fetal surgery group [33, 46, 47].
Comparison of spina bifida subtypes. Rumruay/
Posterior fossa anomalies are characterized by neurodevelopmental malformations in the posterior fossa of the skull cranial cavity. Posterior fossa anomalies are some of the most frequent indications for fetal MRI, occurring in approximately 1 in 5000 live births, encompass a broad spectrum of conditions, and can be categorized as developmental disruptions and malformations [48, 49]. Posterior fossa anomalies include: mega cisterna magna, Blake’s pouch cyst, Dandy-Walker malformation, arachnoid cyst, Joubert syndrome, rhombencephalosynapsis, and Chiari malformation [50]. The malformations can present with either an enlarged cyst appearing with abnormally high retrocerebellar fluid, such as in Dandy-Walker malformation, mega cisterna magna, and Blake’s pouch cyst. Or the malformations cause an unusually small posterior fossa such as in Dandy-Walker variant [51, 52]. The most common reported malformation is generally Dandy-Walker malformation, presenting with macrocephaly in 90–100% of children within months of delivery [49]. Comparison of fetal MRI and fetal ultrasound images in the diagnosis of Dandy-Walker malformation is shown in Figure 3. Prognosis of these conditions is highly influenced by concomitant anomalies, with co-occurring conditions like agenesis and cerebral hypoplasia often resulting in cognitive impairment. Other conditions like mega cisterna magna without hydrocephalus typically result in normal development [50]. In a USA retrospective cohort for ultrasonography referrals for fetal MRI involving posterior fossa anomalies (n = 180), the most common indications for fetal MRI were Dandy-Walker continuum (Dandy-Walker malformation in addition to Dandy-Walker variant) at 42%, mega cisterna magna at 22%, with a change in diagnosis in 70% of cases, and 60% agreement between fetal MRI and postnatal MRI [54].
Dandy-Walker malformation in a 26 week fetus, first suspected as Dandy-Walker variant with ultrasonography, and confirmed as Dandy-Walker malformation with T2W HASTE MRI. A) Ultrasonography illustrating mild ventriculomegaly B) ultrasonography image illustrating cisterna magna that is abnormally large. C) MRI image illustrating direct connection between the cisterna magna and 4th ventricle. D) Sagittal MRI of abnormally large posterior fossa. Reprint Sohn et al., 2008 under CC BY-NC 3.0 [
The corpus callosum is a white matter commissural nerve tract, connecting cortical regions of left and right hemispheres, and composed of myelinated axons that allow action potential propagation [55]. The corpus callosum forms between gestational weeks 11–22, is composed of five distinct regions, and hyperplasia or hypoplasia of these regions is termed callosal dysgenesis, while total absence is deemed callosal agenesis [56]. Agenesis of the corpus callosum rarely occurs in complete isolation, and generally occurs in combination with other disorders. MRI can provide more detail for the extent of the condition than ultrasonography alone [55]. This allows confirmation that the corpus callosum is intact and visualization of co-occurring and associated malformations [9]. Diffusion tensor imaging and fiber tractography in developing research applications has greatly improved the understanding of the neuronal tracts of the corpus callosum, and complications associated with different degrees of agenesis [55]. Tractography has allowed characterization of normal developmental patterns for the nerve bundles of the corpus callosum with increasing gestational age, showing an increase in volume and fractional anisotropy, with a decrease in apparent diffusion coefficient [57].
In twin-to-twin transfusion syndrome, unequal blood supply to the fetuses leads to demise of one twin. Untreated cases have dismal survival rates [58]. The condition indicates diagnostic fetal MRI due to improved capabilities over ultrasonography for identifying ischemic lesions and neurodevelopmental abnormalities. The condition often warrants intervention including serial amniocentesis or
Ultrasonography is the primary imaging modality for monitoring and diagnosis in both congenital and acquired pediatric heart disease and antenatal complications [61]. Ultrasonography and MRI have been determined safe for fetal imaging, but suggested to be used prudently, with common concerns and power limits due to potential tissue heating and acoustic damage [62]. Fetal cardiac MRI can improve outcomes by allowing earlier preparation of treatment procedures [63]. The American Heart Association (AHA) and British Association of Perinatal Medicine (BAPM) suggest neonatal MRI for newborn patients with high-risk CHD in combination of evidence for intracranial hemorrhaging or parenchymal brain trauma, though not recommended for routine use for CHD [9].
CHD is the most common form of congenital abnormalities, occurring in about 0.6–0.8% of live births, with as much as half of the patients requiring open-heart surgery, and is associated with high rates of neurodevelopmental problems [9]. CHD is associated with high neonatal morbidity, particularly in preterm infants [64]. Some of the most common congenital heart abnormalities include atrial septal defects, ventricular septal defects, Tetralogy of Fallot, patent ductus arteriosus, and pulmonary stenosis [65, 66]. A depiction of several types of congenital heart defects is shown in Figure 4. Ventricular septal defects are the most common congenital cardiac anomaly, often requiring surgical repair, though a high percentage will also spontaneously close with age [66, 67, 68].
Illustration of common congenital heart defects. N.Style/
Prenatal cardiac MRI for CHD has generally been limited to a research setting [69]. This has been due to factors including inability to perform electrocardiogram gating, fetal motion, insufficient safety data, and the relatively small size of the features of the fetal heart [70, 71]. Prenatal cardiac MRI allows evaluation of cardiac anatomy, cardiac function, vascular anatomy, flow quantification, and oxygen content [69].
Recent advances has allowed image reconstruction techniques to obtain high-resolution 3D MRI of the fetal heart to assess for congenital heart defects. 3D MRI with motion-corrected image registration was shown in a cohort study to significantly increase visualization and diagnosis of major fetal vascular heart defects in late-gestational age fetuses, when compared to 2D MRI [72]. Additionally, Doppler ultrasonography has shown capable of performing cardiac gating of the fetal heart to generate high-quality bSSFP cine images [73].
A cohort study reported the use of a non-contrast velocity-selective arterial spin labelling (VSASL) sequence to assess placental perfusion in fetuses with CHD compared to fetuses without CHD [74]. The study found decreased global perfusion and increased variation of regional perfusion were linked to increasing gestational age in CHD fetuses. The results also suggest that early placental perfusion may increase to compensate for the heart defect.
A Chinese retrospective study reported findings in 1379 confirmed cases for fetal cardiac MRI from 2005 to 2019, referred after echocardiography could not show the four cardiac chambers in addition to ventricular outflow [75]. Imaging sequences were SSFP, real-time cine SSFP, non-gated phase contrast sequences, and SSTSE. The findings were normal in 92.5% of cases, 5.1% presented with CHD, and 2.4% were diagnosed with an alternative heart condition. In the CHD cases, 56% received correct diagnosis with MRI, which was similar to other studies, as prenatal detection rates for CHD for patients that eventually underwent congenital heart surgery, have tended to be low and less than 50% [76].
Most conditions are best treated when the fetus is delivered at term; however, certain instances warrant the use of
Again, ultrasonography is recommended as the first imaging modality, but MRI is often indicated in a variety of maternal obstetric and non-obstetric complications during pregnancy, including placental adhesive disorders, placental abruption, prognosis of uterine rupture, restricted circulation in placental bed disorders, placental insufficiency, acute appendicitis during pregnancy, prediction of preterm labor, ovarian cysts, and urolithiasis [18, 81]. Additionally, MRI is indicated in treatment planning for difficult deliveries, such as those that require the EXIT procedure due to fetal airway obstruction [9]. Moreover, the technique has proved useful in risk scoring for massive intraoperative hemorrhage in patients with previous cesarean sections and exhibiting placenta previa and accreta [82]. Fetal MRI was recently used in a randomized control trial to assess fetal neurodevelopmental improvement for supplemental pomegranate juice in pregnancies with intrauterine growth restriction [83].
Prenatal MRI is useful for diagnosis of complications associated with maternal viral infections, including the more recent complications associated with SARS-CoV-2 infection.
A variety of fetal complications arising from viral infection can be imaged with MRI, particularly for identifying neurological sequelae, but also for conditions including fetal ascites, hydrops, cardiomegaly, and pericardial effusion [84]. Fetal MRI can be indicated for diagnosis of suspected neurotropic pathogens, such as cytomegalovirus, Zika virus, and toxoplasmosis [85, 86, 87, 88]. Cytomegalovirus is a member of the Herpesviridae family, the most common vertically transmitted congenital viral infection, and the most common infection that results in deafness and intellectual disability in children [89, 90]. MRI and ultrasonography can identify fetal brain lesions resulting from cytomegalovirus infection. MRI diagnosis of infection-related complications allows the possibility of treatment planning for investigational therapies, including antiviral therapy such as Valaciclovir or hyperimmunoglobulin therapy, in the neonates and in fetuses [18, 91, 92].
SARS-CoV-2 is a positive sense, lipid-enveloped, single-stranded, RNA coronavirus that causes both upper and lower respiratory tract infection, which can result in severe pulmonary inflammation and pneumonia, in a condition denoted human coronavirus disease or more recently COVID-19 [93, 94, 95].
SARS-CoV-2 relies upon two types of entry pathways to enter cells through the interaction of the virion spike (S) protein with angiotensin-converting enzyme 2 (ACE2), with release of internal RNA within the cell occurring after cleavage of the S-protein subunits [95]. After binding to ACE2, if transmembrane protease serine 2 (TMPRSS2) is present on the cell surface, the cleavage event occurs through TMPRSS2 and furin, initiating membrane fusion and fusion pore formation on the cell membrane, and release of viral RNA into the cellular cytoplasm [95]. Alternatively, if little or no TMPRSS2 is present on the surface, the clathrin-mediated endocytosis occurs and the virus is internalized intracellularly within endolysosomes, followed by a cathepsin-cleavage event within the endosome, resulting in membrane fusion and release of the viral RNA into the cell cytoplasm [95].
The BNT162b2 (Pfizer, BioNTech) and Spikevax (Moderna, NIAID) are both mRNA-based vaccines that encompass an mRNA strand encoding the spike protein for the original Wuhan-Hu-1 strain, in a liposomal mRNA-lipid nanoparticle, which has a notable ability for large-scale production [95, 96]. The vaccine causes cells to encode the vaccine mRNA to produce spike proteins that are then expressed into the cell membrane. This causes an antibody response that identify these spike protein antigens as a foreign body, stimulating a B-cell and T-cell lymphocyte response to produce antibodies that will tag future spike proteins from SARS-CoV-2 viremia [97]. The viral mutations of these spike protein antigens result in reduced efficacy of the vaccines to induce a immunogenic response. Because mRNA vaccines require antibody neutralization of viremia, mutations in the spike proteins can allow variants to exhibit resistance to the vaccines, potentially causing more severe infections, higher transmissibility, and the possibility of re-infection in vaccinated individuals [98, 99].
A prospective U.K. cohort found 0.5% incidence of SARS-CoV-2 infection during pregnancy that required hospital admission (n = 427) [100]. Of the patients that delivered or experienced pregnancy loss at the time of the article (n = 262), 10% required intensive care unit (ICU) admission and death occurred in 1.2%. From the SARS-CoV-2 positive pregnancies with live born births, 59% had cesarean deliveries and 25% of neonates were admitted to the neonatal intensive care unit (NICU). Preterm delivery occurred in 25% of cases, most of which were induced labor due to COVID-19 complications, and 5% of neonates were COVID-19 positive within 12 hours of birth.
Pregnant women are at high risk of developing severe COVID-19 compared to non-pregnant women, in terms of adjusted risk. Comparing COVID-19 positive pregnancies with non-COVID-19 pregnancies, studies have observed a factor of 3 increase in ICU admissions and invasive intubation with mechanical ventilation, a factor of 2.4 increase in odds for extracorporeal membrane oxygenation, and 70% increase in death [101]. Severe COVID-19 complications are linked with increased rates of preterm birth, hypertensive disorders, and cesarean births [101]. Studies have linked COVID-19 with significant increased mortality for mothers post-delivery and in neonates; particularly for symptomatic patients and those with underlying comorbidities [102, 103]. Neonatal outcomes have been reported as generally favorable, with about half of cases being asymptomatic; though, neonates and children less than one year of age are thought to possibly exhibit higher risk of acute respiratory failure than other children [104].
Risk of vertical transmission of SARS-CoV-2 from mother to fetus is considered low, with the primary transmission to the neonate being through horizontal transmission [101, 105]. Although, at least one case study has confirmed vertical transplacental transmission [106]. There is little evidence for transmission of SARS-CoV-2 through breast milk to the neonate, but pasteurization has been shown to inactivate the SARS-CoV-2 virus and might be considered in specific cases for positive SARS-CoV-2 mothers [101, 105, 107]. Transmission between members of the same family cluster is the primary means of infection from SARS-CoV-2 in children [108]. Infection in children and adolescents has tended to result in milder symptoms and good prognosis, in general [109].
The American College of Radiology (ACR) has suggested limiting the use of MRI to only cases that are absolutely necessary, for COVID-19 positive patients and those suspected of infection [110]. The use of fetal MRI for COVID-19 positive mothers does not have a common indication for routine use and has mostly been reported as case studies or small cohorts. Fetal MRI has been used in cohorts to assess possible neurodevelopmental damage in the fetuses of mothers with SARS-CoV-2 infection during early pregnancy, with results showing no abnormal findings [111]. However, a case study of
A significant increase in obstetrical complications in COVID-19 has been observed, compared to non-COVID-19 pregnancies. Studies have shown higher rates of fetal deaths, maternal deaths, ICU admissions, preterm births, and cesarean deliveries. These outcomes highlight the benefit of vaccination during pregnancy, to reduce the risk of maternal and fetal complications [101].
Prenatal MRI offers useful complementary diagnostic information to ultrasonography, particularly for neurodevelopmental complications. The technique can be used for diagnosis, for guiding treatment decisions, and to counsel parents for scenarios like potential termination. MRI has been determined safe for fetal health, though low field strengths and non-contrast imaging are generally used, as these scenarios are lower risk to the fetus. MRI can improve diagnostic accuracy for neurodevelopmental and cardiac anomalies when used in conjunction with ultrasonography, but factors like additional cost limits the number of indications for prenatal diagnosis. Studies have shown increased rates of pregnancy-related complications in patients infected with SARS-CoV-2 during pregnancy. Although, studies with fetal MRI for assessing fetal developmental complications due to maternal COVID-19 has been limited, but results have been reported in case studies and small cohorts.
Thanks to the Center for Biomedical Imaging and the Image-guided Interventions Laboratory for supporting the development of this manuscript. Thanks to Dr. Daniela Dumitriu LaGrange for reviewing the manuscript and suggesting improvements.
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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Keith Harrison and Brandon Martin",authors:[{id:"106505",title:"Dr.",name:"C. Keith",middleName:null,surname:"Harrison",slug:"c.-keith-harrison",fullName:"C. Keith Harrison"},{id:"106509",title:"Dr.",name:"Brandon",middleName:null,surname:"Martin",slug:"brandon-martin",fullName:"Brandon Martin"}]},{id:"51754",doi:"10.5772/64511",title:"Analytic Hierarchy Process Application in Different Organisational Settings",slug:"analytic-hierarchy-process-application-in-different-organisational-settings",totalDownloads:2210,totalCrossrefCites:7,totalDimensionsCites:7,abstract:"Purpose – The purpose of this paper is to apply AHP in two case settings which include (i) evaluation/selection of maintenance policy (ii) sustainability factors of employee suggestion schemes.",book:{id:"5142",slug:"applications-and-theory-of-analytic-hierarchy-process-decision-making-for-strategic-decisions",title:"Applications and Theory of Analytic Hierarchy Process",fullTitle:"Applications and Theory of Analytic Hierarchy Process - Decision Making for Strategic Decisions"},signatures:"Damjan Maletič, Flevy Lasrado, Matjaž Maletič and Boštjan\nGomišček",authors:[{id:"178809",title:"Prof.",name:"Boštjan",middleName:null,surname:"Gomišček",slug:"bostjan-gomiscek",fullName:"Boštjan Gomišček"}]},{id:"50912",doi:"10.5772/64022",title:"Analytic Hierarchy Process Applied to Supply Chain Management",slug:"analytic-hierarchy-process-applied-to-supply-chain-management",totalDownloads:2524,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Resource allocation (RA) and supplier selection (SS) are two major decision problems regarding supply chain management (SCM). A supply chain manager may solve these problems by considering a single criterion, for instance, costs, customer satisfaction, or delivery time. Applying analytic hierarchy process (AHP), the supply chain manager may combine such criteria to enhance a compromised solution. This chapter presents AHP applications to solve two real SCM problems faced by Brazilian companies: one problem regarding the RA in the automotive industry and another one to SS in a chemical corporation.",book:{id:"5142",slug:"applications-and-theory-of-analytic-hierarchy-process-decision-making-for-strategic-decisions",title:"Applications and Theory of Analytic Hierarchy Process",fullTitle:"Applications and Theory of Analytic Hierarchy Process - Decision Making for Strategic Decisions"},signatures:"Valerio Antonio Pamplona Salomon, Claudemir Leif Tramarico and\nFernando Augusto Silva Marins",authors:[{id:"137460",title:"Dr.",name:"Fernando",middleName:null,surname:"Marins",slug:"fernando-marins",fullName:"Fernando Marins"},{id:"179921",title:"Dr.",name:"Valerio",middleName:"A. 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Hellsten",authors:[{id:"111970",title:"Dr.",name:"Laurie-Ann",middleName:null,surname:"Hellsten",slug:"laurie-ann-hellsten",fullName:"Laurie-Ann Hellsten"}]},{id:"51007",doi:"10.5772/63686",title:"AHP‐Aided Evaluation of Logistic and Transport Solutions in a Seaport",slug:"ahp-aided-evaluation-of-logistic-and-transport-solutions-in-a-seaport",totalDownloads:1813,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The chapter reports on the application of the analytic hierarchy process (AHP) to a strategic decision in the transport sector, concerning the reconfiguration of the railway infrastructure of the seaport of Trieste. The proposed solutions should not only solve some technical and operational problems of the terminal, but they could allow the port to be included in the Trans‐European Network‐Transport Programme (TEN‐T), promoted by the European Union and aimed to develop the Trans‐European Networks of Transport. Accordingly, the selection of the solution with the most promising potential to satisfy the goals of the TEN‐T policy is a fundamental stage of the project. The case study is an actual AHP application to an evaluation process concerning a pre‐feasibility study of strategic solutions in the logistics and transport fields. Some practical aspects regarding the application of the AHP and the building of the model, when several stakeholders are involved in the decision process, are highlighted and discussed.",book:{id:"5142",slug:"applications-and-theory-of-analytic-hierarchy-process-decision-making-for-strategic-decisions",title:"Applications and Theory of Analytic Hierarchy Process",fullTitle:"Applications and Theory of Analytic Hierarchy Process - Decision Making for Strategic Decisions"},signatures:"Cristian Giacomini, Giovanni Longo, Alice Lunardi and Elio Padoano",authors:[{id:"181593",title:"Prof.",name:"Elio",middleName:null,surname:"Padoano",slug:"elio-padoano",fullName:"Elio Padoano"},{id:"182135",title:"Prof.",name:"Giovanni",middleName:null,surname:"Longo",slug:"giovanni-longo",fullName:"Giovanni Longo"},{id:"185623",title:"Dr.",name:"Cristian",middleName:null,surname:"Giacomini",slug:"cristian-giacomini",fullName:"Cristian Giacomini"},{id:"185625",title:"BSc.",name:"Alice",middleName:null,surname:"Lunardi",slug:"alice-lunardi",fullName:"Alice Lunardi"}]}],mostDownloadedChaptersLast30Days:[{id:"51421",title:"A Case Study on the Application of the Analytic Hierarchy Process (AHP) to Assess Agri-Environmental Measures of the Rural Development Programme (RDP 2007–2013) in Slovenia",slug:"a-case-study-on-the-application-of-the-analytic-hierarchy-process-ahp-to-assess-agri-environmental-m",totalDownloads:2306,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The reform of the Common Agricultural Policy (CAP) in 2003 focused mainly on the economic and environmental challenges. The Rural Development Programme 2007–2013, hereafter RDP, being implemented in Slovenia is therefore aiming at promoting proposed activities that help to improve the rural areas. Agri-environmental measures (AEMs) encourage farmers to make an environmental commitment for a period of at least 5 years aiming at preserving the environment and maintaining the countryside. Because of practising environmental friendly production methods, the farmers might be encountered with more costs and reduction of yield. Therefore, payments are made as compensation. Concentrating only on one of the four pillars of the RDP, “Improvement of environment and the countryside”, this paper attempts to assess the Slovenian agri-environmental measures with the help of the multicriteria decision analysis, that is, analytic hierarchy process (AHP) and its supporting software Expert Choice™. In the presented case study, three main criteria and their attributes were determined. With the help of experts (questionnaires), data were collected, which made the assessment possible. The results show that organic fruit, vine and horticultural production are seen as the most important AEM. This is specific for the Republic of Slovenia because of its large amount of area designated as least favoured areas (LFA) that are not suitable for arable farming.",book:{id:"5142",slug:"applications-and-theory-of-analytic-hierarchy-process-decision-making-for-strategic-decisions",title:"Applications and Theory of Analytic Hierarchy Process",fullTitle:"Applications and Theory of Analytic Hierarchy Process - Decision Making for Strategic Decisions"},signatures:"Monica Huehner, Črtomir Rozman and Karmen Pažek",authors:[{id:"179642",title:"Prof.",name:"Karmen",middleName:null,surname:"Pažek",slug:"karmen-pazek",fullName:"Karmen Pažek"}]},{id:"33747",title:"What Do We Know About Time Management? A Review of the Literature and a Psychometric Critique of Instruments Assessing Time Management",slug:"what-do-we-know-about-time-management-a-review-of-the-literature-and-a-psychometric-critique-of-inst",totalDownloads:35360,totalCrossrefCites:0,totalDimensionsCites:5,abstract:null,book:{id:"1854",slug:"time-management",title:"Time Management",fullTitle:"Time Management"},signatures:"Laurie-Ann M. Hellsten",authors:[{id:"111970",title:"Dr.",name:"Laurie-Ann",middleName:null,surname:"Hellsten",slug:"laurie-ann-hellsten",fullName:"Laurie-Ann Hellsten"}]},{id:"51359",title:"Application of the AHP Method in Environmental Engineering: Three Case Studies",slug:"application-of-the-ahp-method-in-environmental-engineering-three-case-studies",totalDownloads:2216,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"The chapter presents the application of the Analytic Hierarchy Process (AHP) method in the field of environmental management. The work shows how to use the results of environmental engineering tools or models as an input for the AHP method. Three case studies are presented: selection of the best municipal solid waste disposal system, assessment of the tap and bottled water consumption on the environment, and selection of the heat pump for the individual home. In the first case study, the AHP analysis was required to assess the environmental impact of waste disposal system. This was done by the use of Integrated Waste Management model (IWM-1), which delivered results aggregated, at the next step, into Life Cycle Analysis (LCA) categories. The obtained results were used in the AHP analysis to choose the best scheme for the waste disposal system. In the second case study, the AHP method was used to evaluate different patterns of water drinking. Obtained results help decision makers in assessing regional and individual environmental impact if the drinking pattern changes. Selected evaluation criteria were solid waste stream, energy consumption, carbon dioxide emission, and Eco-indicator 99 H/A points. The third case study presents the method of heat pump selection. The environmental performance criteria were developed using the criteria of the ecolabeling program. All three case studies are based on real data.",book:{id:"5142",slug:"applications-and-theory-of-analytic-hierarchy-process-decision-making-for-strategic-decisions",title:"Applications and Theory of Analytic Hierarchy Process",fullTitle:"Applications and Theory of Analytic Hierarchy Process - Decision Making for Strategic Decisions"},signatures:"Tomasz Stypka, Agnieszka Flaga-Maryańczyk and Jacek Schnotale",authors:[{id:"179383",title:"Dr.",name:"Tomasz",middleName:null,surname:"Stypka",slug:"tomasz-stypka",fullName:"Tomasz Stypka"},{id:"179392",title:"Dr.",name:"Agnieszka",middleName:null,surname:"Flaga-Maryańczyk",slug:"agnieszka-flaga-maryanczyk",fullName:"Agnieszka Flaga-Maryańczyk"},{id:"179695",title:"Prof.",name:"Jacek",middleName:null,surname:"Schnotale",slug:"jacek-schnotale",fullName:"Jacek Schnotale"}]},{id:"68601",title:"How Does Socio-Technical Approach Influence Sustainability? Considering the Roles of Decision Making Environment",slug:"how-does-socio-technical-approach-influence-sustainability-considering-the-roles-of-decision-making-",totalDownloads:772,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Aim/purpose: the current study explains the mediation of ERP in the role of a socio-technical approach and decision-making with firms’ sustainable performance. Background: despite the existence of existing literature on success and failure factors of ERP, the current work highlights the impact of socio-technical factors and decision-making environment on ERP success. Additionally, the weak research work regarding the mediation of ERP is addressed here in this study and has tried to fill the mentioned gap. Contribution: the most important contribution of the study is assessing the mediating role of the ERP system in the linkage of decision-making environment and socio-technical factors. Moreover, the work contributes by examining the moderation of organizational culture while relating the socio-technical environment and ERP system. Findings: the study finds that there is a significant role of ERP as a mediator while relating socio-technical elements and the decision-making environment; however, we do not find any significant moderation of organizational culture in the linkage of ERP system and socio-technical elements. Impact on Society: the societal implication of the study is that it provides a reference for the firms having the same cultural characteristics while using ERP to overcome the issue of pollution in Iraq.",book:{id:"9332",slug:"application-of-decision-science-in-business-and-management",title:"Application of Decision Science in Business and Management",fullTitle:"Application of Decision Science in Business and Management"},signatures:"Hadi AL-Abrrow, Alhamzah Alnoor, Hasan Abdullah and Bilal Eneizan",authors:[{id:"303565",title:"Prof.",name:"Hadi",middleName:null,surname:"Al-Abrrow",slug:"hadi-al-abrrow",fullName:"Hadi Al-Abrrow"},{id:"303609",title:"Mr.",name:"Alhamzah",middleName:null,surname:"Alnoor",slug:"alhamzah-alnoor",fullName:"Alhamzah Alnoor"},{id:"303612",title:"Mr.",name:"Hasan",middleName:null,surname:"Abdullah",slug:"hasan-abdullah",fullName:"Hasan Abdullah"},{id:"307559",title:"Dr.",name:"Bilal",middleName:null,surname:"Eneizan",slug:"bilal-eneizan",fullName:"Bilal Eneizan"}]},{id:"50912",title:"Analytic Hierarchy Process Applied to Supply Chain Management",slug:"analytic-hierarchy-process-applied-to-supply-chain-management",totalDownloads:2524,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Resource allocation (RA) and supplier selection (SS) are two major decision problems regarding supply chain management (SCM). A supply chain manager may solve these problems by considering a single criterion, for instance, costs, customer satisfaction, or delivery time. Applying analytic hierarchy process (AHP), the supply chain manager may combine such criteria to enhance a compromised solution. 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