Complications of vascular access
\\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:"3361",leadTitle:null,fullTitle:"Regenerative Medicine and Tissue Engineering",title:"Regenerative Medicine and Tissue Engineering",subtitle:null,reviewType:"peer-reviewed",abstract:"Few events in science have captured the same level of sustained interest and imagination of the nonscientific community as Stem Cells, Tissue Engineering, and Regenerative Medicine. The fundamental concept of Tissue Engineering and Regenerative Medicine is appealing to scientists, physicians, and lay people alike: to heal tissue or organ defects that the current medical practice deems difficult or impossible to cure. Tissue engineering combines cells, engineering, and materials methods with suitable biochemical and physiochemical factors to improve or replace biologic functions. Regenerative medicine is a new branch of medicine that attempts to change the course of chronic disease, in many instances regenerating failing organ systems lost due to age, disease, damage, or congenital defects. The area is rapidly becoming one of the most promising treatment options for patients suffering from tissue failure. This book of Regenerative Medicine and Tissue Engineering fairly reflects the state of the art of these two disciplines at this time as well as their therapeutic application. It covers numerous topics, such as stem cells, cell culture, polymer synthesis, novel biomaterials, drug delivery, therapeutics, and the creation of tissues and organs. The goal is to have this book serve as a reference for graduate students, post-docs, teachers, scientists and physicians, and as an explanatory analysis for executives in biotech and pharmaceutical companies.",isbn:null,printIsbn:"978-953-51-1108-5",pdfIsbn:"978-953-51-4248-5",doi:"10.5772/46192",price:169,priceEur:185,priceUsd:219,slug:"regenerative-medicine-and-tissue-engineering",numberOfPages:868,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"fe914d49a96b3dcd00d27292ae23536e",bookSignature:"Jose A. 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Andrades completed his doctorate in Cellular Biology by the University of Málaga (Spain). He has been a Post-Doctoral fellow and Visiting Professor at Children’s Hospital Los Angeles, University of Southern California (Los Angeles, CA), as well as at the Skeletal Research Center, Case Western Reserve University (Cleveland, OH). He currently has a faculty position at the Department of Cell Biology, Genetics and Physiology (Laboratory of Bioengineering and Tissue Regeneration) at the University of Málaga. Dr. Andrades leads grants, and is author of scientific publications, focused on the study of the chondro-osteo-tendinogenesis by using mesenchymal stem cells, growth factors with specific molecular domains, and different biomaterials, for skeletal tissue engineering. The group has developed patents on cellular procedures that allow regeneration in bone/articular cartilage lesions of live animals. Currently, Dr. Andrades is coordinator of the Cellular Therapy Program NACRE (New Approaches for Cartilage Regeneration) in the CIBER-BBN. He belongs to the TerCel Network, and to the NanomedSpain, in which consortia develops collaborations with several groups of physicians for the clinical translation of their studies.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Malaga",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"980",title:"Tissue Engineering and Regenerative Medicine",slug:"tissue-engineering-and-regenerative-medicine"}],chapters:[{id:"44123",title:"Placenta-Derived Stem Cells as a Source for Treatment of Lung and Liver Disease in Cystic 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Blood transfusion medicine has become a sophisticated and specialized field of medicine. Some aspects will be discussed in this book. The book has been divided into three sections. The first section includes chapters describing the immunological and coagulation-assisting functions of red blood cells and methods to measure their life span. The second section discusses the role of platelets in inflammatory processes. The third section reviews functional dose of RBC transfusions and transfusion practice in various clinical settings.",isbn:"978-953-51-3320-9",printIsbn:"978-953-51-3319-3",pdfIsbn:"978-953-51-4759-6",doi:"10.5772/66265",price:119,priceEur:129,priceUsd:155,slug:"transfusion-medicine-and-scientific-developments",numberOfPages:128,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"b5a95b51b34becb58f940bdc6cc2c26e",bookSignature:"A.W.M.M. Koopman-van Gemert",publishedDate:"July 5th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5965.jpg",keywords:null,numberOfDownloads:11230,numberOfWosCitations:5,numberOfCrossrefCitations:6,numberOfDimensionsCitations:9,numberOfTotalCitations:20,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 8th 2016",dateEndSecondStepPublish:"November 29th 2016",dateEndThirdStepPublish:"February 25th 2017",dateEndFourthStepPublish:"May 26th 2017",dateEndFifthStepPublish:"July 25th 2017",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"105746",title:"Dr.",name:"A.W.M.M.",middleName:null,surname:"Koopman-van Gemert",slug:"a.w.m.m.-koopman-van-gemert",fullName:"A.W.M.M. Koopman-van Gemert",profilePictureURL:"https://mts.intechopen.com/storage/users/105746/images/5803_n.jpg",biography:"Dr. Anna Wilhelmina Margaretha Maria Koopman-van Gemert MD, PhD, became anaesthesiologist-intensivist from the Radboud University Nijmegen (the Netherlands) in 1987. She worked for a couple of years also as a blood bank director in Nijmegen and introduced in the Netherlands the Cell Saver and blood transfusion alternatives. She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Albert Schweitzer Hospital",institutionURL:null,country:{name:"Gabon"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1030",title:"Immunohaematology",slug:"immunohaematology"}],chapters:[{id:"55513",title:"A Double In Vivo Biotinylation Technique to Assess Erythrocyte Turnover in Blood Circulation",slug:"a-double-in-vivo-biotinylation-technique-to-assess-erythrocyte-turnover-in-blood-circulation",totalDownloads:1575,totalCrossrefCites:0,authors:[{id:"202626",title:"Prof.",name:"Rajiv",surname:"Saxena",slug:"rajiv-saxena",fullName:"Rajiv Saxena"}]},{id:"55207",title:"Immunocamouflaged RBC for Alloimmunized Patients",slug:"immunocamouflaged-rbc-for-alloimmunized-patients",totalDownloads:1545,totalCrossrefCites:1,authors:[{id:"202243",title:"Dr.",name:"Mark",surname:"Scott",slug:"mark-scott",fullName:"Mark Scott"},{id:"205640",title:"BSc.",name:"Wendy",surname:"Toyofuku",slug:"wendy-toyofuku",fullName:"Wendy Toyofuku"},{id:"205641",title:"BSc.",name:"Xining",surname:"Yang",slug:"xining-yang",fullName:"Xining Yang"},{id:"205642",title:"Dr.",name:"Meera",surname:"Raj",slug:"meera-raj",fullName:"Meera Raj"},{id:"205643",title:"Dr.",name:"Ning",surname:"Kang",slug:"ning-kang",fullName:"Ning Kang"}]},{id:"55954",title:"Red Blood Cells and Relation to Thrombosis",slug:"red-blood-cells-and-relation-to-thrombosis",totalDownloads:2067,totalCrossrefCites:4,authors:[{id:"202814",title:"Associate Prof.",name:"Anil",surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}]},{id:"55635",title:"Platelet and Immunity in Transfusion Medicine",slug:"platelet-and-immunity-in-transfusion-medicine",totalDownloads:1464,totalCrossrefCites:1,authors:[{id:"200979",title:"Prof.",name:"Xingbin",surname:"Hu",slug:"xingbin-hu",fullName:"Xingbin Hu"},{id:"206182",title:"Ms.",name:"Jinmei",surname:"Xu",slug:"jinmei-xu",fullName:"Jinmei Xu"}]},{id:"55343",title:"Red Blood Cell Transfusion and Functional Dose",slug:"red-blood-cell-transfusion-and-functional-dose",totalDownloads:1289,totalCrossrefCites:0,authors:[{id:"202960",title:"Prof.",name:"Deqing",surname:"Wang",slug:"deqing-wang",fullName:"Deqing Wang"},{id:"202995",title:"Dr.",name:"Leiying",surname:"Zhang",slug:"leiying-zhang",fullName:"Leiying Zhang"}]},{id:"55676",title:"Transfusion in Transplantation",slug:"transfusion-in-transplantation",totalDownloads:1878,totalCrossrefCites:0,authors:[{id:"94230",title:"Prof.",name:"Guray",surname:"Saydam",slug:"guray-saydam",fullName:"Guray Saydam"},{id:"94231",title:"Prof.",name:"Fahri",surname:"Sahin",slug:"fahri-sahin",fullName:"Fahri Sahin"},{id:"202813",title:"M.D.",name:"Eren",surname:"Arslan Davulcu",slug:"eren-arslan-davulcu",fullName:"Eren Arslan Davulcu"}]},{id:"55256",title:"Red Blood Cell Transfusion Strategy for Upper Gastrointestinal Bleeding",slug:"red-blood-cell-transfusion-strategy-for-upper-gastrointestinal-bleeding",totalDownloads:1413,totalCrossrefCites:0,authors:[{id:"197501",title:"Dr.",name:"Xingshun",surname:"Qi",slug:"xingshun-qi",fullName:"Xingshun Qi"},{id:"205228",title:"Prof.",name:"Fernando",surname:"Romeiro",slug:"fernando-romeiro",fullName:"Fernando Romeiro"},{id:"207599",title:"Prof.",name:"Yiling",surname:"Li",slug:"yiling-li",fullName:"Yiling Li"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"177731",firstName:"Dajana",lastName:"Pemac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/177731/images/4726_n.jpg",email:"dajana@intechopen.com",biography:"As a Commissioning Editor at IntechOpen, I work closely with our collaborators in the selection of book topics for the yearly publishing plan and in preparing new book catalogues for each season. 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Hemodialysis is the most preferable modality among them [4], making a suitable permanent vascular access (VA) vital for their treatment. The ultimate purpose is the successful creation of a well-functioning, long-lasting VA, capable of delivering adequate dialysis to the patient with the minimum of complications under its appropriate management. In the last years in this field of nephrology, very few changes have taken place. Three types of permanent VA are in use, arteriovenous fistula (AVF), arteriovenous grafts (AVGs), and cuffed central venous catheters (CVCs). Long-lasting survival, adequate blood flow, and low complications rate are necessary characteristics of them. Native forearm AVF best fulfills this criteria and is the first choice of VA, the first native arteriovenous fistula (AVF) described in 1966 by Brescia and Chimino [5]. The second choice is upper arm AVF, followed by AVG and last one cuffed CVC [6–8]. Vascular access dysfunction is responsible for 20% of dialysis patients’ hospitalizations in the USA [9], making it one of the most important causes of morbidity [10], while the annual cost of VA creation and maintenance is over 1 billion dollars yearly [11], with arteriovenous graft (AVG) cost be more than fivefold higher than AVF [12]. Thus, VA is called the “Achilles’ heel” of hemodialysis [13].
In 1924, Haas [14] carried out the first hemodialysis treatment in humans using glass needles in radial and cubital vein. In 1943, Kolff used venipuncture needles in the femoral artery and vein [15, 16]. Kolff’s [17] twin-coil kidney made regular hemodialysis treatments possible in 1950s, making the need of a safe, reliable, long-lasting VA more imperative.
Aubaniac [18], in 1952, described the puncture of subclavian vein as a VA, while, in the 1960s, Dillard, Quinton, and Scribner [19], based on Alwall’s experience, developed arteriovenous Teflon shunt inserted into radial artery and cephalic vein. Flexible silicon rubber replaced later Teflon. Based on Seldinger’s technique, Shaldon inserted catheters into femoral artery and vein for dialysis sessions in 1961 [20, 21]. Vessels in different sites were used, over time, including the subclavian, jugular, and femoral vein.
Cimino and Brescia [22] described, in 1962, a “simple venipuncture for hemodialysis.” Fogarty et al. [23] invented, in 1963, a special designed catheter for thrombectomy and embolectomy with an inflatable balloon at its distal tip. In 1965, the first AVF was created, and 14 more in 1966 when Brescia, Cimino, Appel, and Hurwich published their paper [24]. Sperling [25], in 1967, created an end-to-end anastomosis in the forearm, between radial artery and cephalic vein, in 15 patients, whereas Appell did side-to-side anastomosis. End-to-end anastomosis usually is not the first choice of AVF due to high risk of steal syndrome in aging, diabetic patients of dialysis, but it remains a useful option in revision procedures, although it is correlated with higher mortality risk from infections [26].
Nowadays, artery side-to-vein anastomosis seems to be a standard procedure [27], which began from Rohl et al. [28] in 1968. Girardet et al. [29] and Brittinger et al. [30] in 1970 described their experience with AVG between femoral vein and artery and subcutaneously fixed superficial femoral artery for chronic HD. Brittinger et al. [31] were the first to implant a plastic valve as a vascular access in an animal model, but unfortunately, their efforts did not proceed to a human one. In the early 1970s, Buselmeier et al. [32] developed a U-shaped silastic prosthetic AV shunt with either one or two Teflon plugged outlets, which communicated to the outside of the body. The U-shaped portion could be totally or partially implanted subcutaneously. Subsequently, pediatric hemodialysis patients were extremely favored by this procedure. In 1976, Baker [33] presented expanded PTFE grafts in 72 hemodialysis patients. In the subsequent years, several publications indicated the benefits and the shortcomings of the prosthetic material in question, remaining the primary choice of graft for hemodialysis VA to date. The same year, two authors, Mindich and Dardik, had worked with a new graft material: the human umbilical cord vein [34, 35]. Regrettably so, this material did not succeed in becoming a revolutionary graft material due to its inadequate resistance against the trauma of repeated cannulations and their complications (aneurysm and infection). After the subclavian route for hemodialysis access was firstly introduced by Shaldon in 1961, it was further processed in 1969 by Josef Erben, using the intraclavicular route [36]. In the next 20 years or so, the subclavian vein was the preferred access for temporary vascular access by central venous catheterization. Today, due to phlebographic studies revealing a 50% stenosis or occlusion rate at the cannulation site, subclavian route has been discarded. Subclavian stenosis and occlusion predispose to edema of the arm, especially after creation of an AV fistula [37].
The first angioplasty described by Dotter et al. [38], who introduced a type of balloon, was immensely conducive to the resolution of one of the most significant predicaments in vascular surgery and vascular access surgery.
In 1977, Gracz et al. [39] created the “proximal forearm fistula for maintenance hemodialysis,” a variant of an AV anastomosis. An adjustment of this AVF became quite significant in the old, hypertensive, and diabetic patients on the grounds that it allows a proximal anastomosis with a low risk of hyper circulation [40]. In 1979, Golding et al. [41] developed a “carbon transcutaneous hemodialysis access device” (CATD), commonly known as “button,” as a blood access not requiring needle puncture. As a procedure of the third choice, these devices were expensive and never gained widespread acceptance. Shapiro et al. [42] described another type of “button,” a device similar to that developed by Golding.
Nowadays, and thanks to all above efforts, nephrologists have the ability to choose the most suitable VA for their patients depending on special needs of each one. Based on expected half-life, the first demarcation is of permanent and temporary VAs [43]. Long-term or permanent VAs are called the ones with an expected half-life of more than 3 years, and mainly include AVF [13] and PTFE AVG. VAs with expected half-life of less than 90 days are called temporary VAs and basically are noncuffed double lumen catheters and arteriovenous shunts. The VAs with half-life between the above categories (90 days to 3 years) are the mid-term VA containing tunneled cuffed catheters, port devices and external and internal shunts.
Acute hemodialysis is a lifesaving treatment, which needs a VA in order to be carried out. When a permanent VA is not available, the preferred and currently available VA for acute hemodialysis is cuffed tunneled and noncuffed nontunneled hemodialysis catheters (Figures 1–5). The reason is that they can be used immediately and placed relatively easily. For catheter insertion, a modified Seldinger guide wire technique is used, preferably with ultrasound guided assistance for minimizing acute placement complications [44, 45].
Noncuffed in jugular double lumen catheter.
Cuffed tunneled in jugular double lumen catheter.
Permanent cuffed jugular catheter.
Acute noncuffed jugular catheter.
Femoral noncuffed catheter.
The most used and feasible are the noncuffed nontunneled catheters with easy insertion and availability for immediate use. They have some specific technical characteristics; they are made of polymers inelastic at room temperature, facilitating the insertion, but unstiffening at inner body temperature in order to be atraumatic for the vessels. The distance between the inflow and the outflow tip of the catheter must be at least 2 cm to lessen recirculation [46].
Central veins such as jugular or femoral can be used as insertion routes of these catheters [47]. Subclavian typically is an option, but due to its higher incidence of complications, such us lung injury, it is used when the others insertion sites are not feasible.
The National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) 2006 guidelines recommend the radiographical identification of tip placement and any potential complications before catheter use or anticoagulation treatment [48]. Subclavian vein should be avoided for catheter insertion due to high frequency of stenosis and thrombosis.
There are restrictions concerning the use of these catheters such as the blood flow with a maximum pump speed of 300 ml/min, although actual blood flow tops at 250 ml/min, catheters for insertion in femoral vein should be no less of 18 to 25 cm long to minimize recirculation [49, 50]. Their insertion site determines their life use, with the ones in internal jugular vein be suitable for use for about 2 to 3 weeks, while in femoral vein are used for 3 to 7 days in bedridden patients and for a single treatment in ambulatory patients [51]. Nevertheless, according to KDOQI guidelines, the life use of noncuffed, nontunneled catheters must be of a week or less; when hemodialysis treatment will be required for a longer period, the placement of cuffed, tunneled catheters is suggested [48]. Especially in hospitalized patients, triple lumen catheters are placed, using the third lumen for intravenous drugs and fluid administration and for blood drawing. It seems that two and three lumen catheters have similar blood flow and inflections incidence [52]. The leader cause for catheter removal is infectious complications.
Taking patient-dependent factors into consideration, such as life expectancy, comorbidities, the status of the venous and arterial vascular system, is very important in order to prescribe the appropriate access. Each type of access, such as arteriovenous fistula (AVF), arteriovenous graft (AVG) or TC, has a different effect on circulatory system, and this should be taken into consideration. Also, the duration of their functionality and the risk for infection and thrombosis are important factors to consider. Each type of surgical anastomosis has advantages and disadvantages [53]. Also, it seems that the advantages of an AVF attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AVF success rate and lower life expectancy, suggesting that vascular access-related outcomes may be optimized by considering individual patient characteristics [54]. The American Association for Vascular Surgery and the Society for Vascular Surgery, in 2002, for better consultation and understanding between physicians and registration of VA set VA reporting standards in which three components should be listed, structure (autogenous, prosthetic), position and alignment (loop, direct, etc.) [55]. Risk factors such as female gender, age, diabetic nephropathy, dialysis initiation via CVC and inability of VA maturation before HD initiation are responsible for the majority of VA failure. Repetitive VA failures are risk factor for mortality [56]. It seems that early referral to nephrologist and patient’s education leads to initiation of dialysis with permanent VA, better metabolic and clinical situation, lower long-term morbidity and higher 2-year survival [57–61]. It is of benefit to the patient to begin hemodialysis treatment via a functional AVF than with a TC [62–64]; however, grafts are a better alternative to TCs, when AVF is not feasible [65]. Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a “personal access solution.” Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of cadaveric organs to patients with precarious vascular access provides a potential solution [66]. Patients who received either femoral AVG or HeRO VA device experience poor access patency. ESRD patients who receive either of these procedures appear to be at the end stage of available access options [67].
The first choice of VA is AVF, for its longevity and low morbidity and mortality rates [68, 69], low complication incidence for infection (one-tenth of AVGs) and thrombosis (one-sixth of AVGs) [70, 71]. AVFs’ primary patency rates at 1 year vary considerably between USA and Europe, with reports from the USA that include diabetic patients be as low as 40–43% [72, 73]. From the study of 748 AVFs in diabetic patients over 5 years, Konner et al. showed a primary patency rate of 69–81% [74], while Chemla et al. had a rate of 80% at 22 months in 552 radiocephalic AVFs in 153 patients over a 4-year period [75]. Hemodialysis patients with AVF have lower mortality and that seems to be attributed not only to decreased incidence of infections and VA dysfunctions but also to other factors, such as LVEF increase and blood pressure and arterial stiffness reduction, as Korsheed et al. [76] showed.
Based on the way of their creation, three types of AVFs can be identified. The first type belongs to the AVFs where an artery and a vein are connected in their natural position, with a side-to-side or side-artery-to-vein-end anastomosis. In the second type, a vein is connected to an artery in end-to-side form, after its metathesis, to connect a further distance or surface the vein to facilitate cannulation; a tunnel creation is required for vein’s new positioning. When a vein is connected to an artery end-to-end after it is removed from its anatomical location, we have the third type of AVF [77] (Figures 6–9). The end-to-end technique is abandoned nowadays since it leads to advanced risk for ischemia and thrombosis. Vein end to artery side anastomosis is the most common technique. The first option for the primary AVF is the radial-cephalic. Distal forearm ulnar-basilic has similar secondary patency rate to it and is the best alternative when the first one is not feasible [78]. Stenosis due to technical problems like false surgical cut of vein leads to dysfunctional VA. Complications such as heart failure or steal syndrome may result from a more proximal, big arterial anastomosis [77]. Local anesthesia is usually effective for AVF creation, and the morbidity of the procedure is low. AVF requires time after its creation for maturation before cannulation for at least 14 days according to DOPPS (Data from the Dialysis Outcomes and Practice Patterns Study). During the period of maturation, the blood flow and the vessel size increase over time in 8–12 weeks, and the initial blood flow is in a range of 200–300 ml/min [64].
Forearm AVF.
Side-to-side forearm AVF.
End-to-end forearm AVF.
Side-to-end forearm AVF.
The placement of AVFs should be initiated when the patient reaches CKD stage 4, or within 1 year of the anticipated start of dialysis. In their recent study, Hod et al. [79] suggested that creating AVF more than 6 to 9 months before initiating dialysis in elderly may not associate with better AVF success rate. In order to increase the possibilities of a well-functioning AVF’s creation and to minimize the complication, a physical examination must be done prior to procedure to identify any differences in blood pressure between the upper extremities [80] and the presence or lack of a well-developed palmar arch to avoid steal syndrome in case of using the dominant artery for AVF creation [81].
Additional information before the creation of AVF can be given with ultrasound of the vessels; their diameter is closely correlated with surgery success with a size of 2 mm and more leads with fruitful maturation [80], in contrast of a size of 1.6 mm and less, which predispose to failure [82]. The upper extremity AVF is the preferred access for hemodialysis, the duplex ultrasound identifies suitable arteries and veins for its successful creation, while early detection and intervention can save the fistula when complications occur [83]. Uzun et al. [84] showed that autologous saphenous vein can be preferably chosen as a prosthetic hemodialysis access graft due to its higher primary and secondary patency and lower complication rate and cost when compared with PTFE grafts. According to the vascular access guidelines of KDOQI, a well-functioning AVF has blood flow over 600 ml/min, with a diameter greater than 6 mm, and is lying less than 6 mm from the surface in a depth between 5 and 10 mm. When an AVF’s maturation progresses successfully, then rapidly after surgery blood flow increases from baseline values of 30 to 50 ml/min, reaching 200 to 800 ml/min within 1 week; after 8 weeks, blood flow is over 480 ml/min [85, 86]. The AVFs must be evaluated 4–6 weeks after placement; experienced examiners (e.g., dialysis nurses) can identify nonmaturing fistulas with 80% accuracy [87]. Patients with newly placed AVF are advised for hand squeezing exercises to increase the rate of fistula maturation, such as squeezing a ball, bicep curls, and finger tips touches resulting to fistulae dilation [88, 89]. Far Infrared therapy, which is a form of heat therapy, has been implicated in improvement of endothelial function and hemodynamics in coronary arteries, probably through up-regulating endothelial nitric oxide synthase (eNOS) expression in arterial endothelium, leading to improved cardiac function in patients with chronic heart diseases. Repeated leg hyperthermia using FIR has been shown to reduce oxidative stress in bed-ridden type II diabetics and may positively influence the complex process of AVF maturation, improving both primary and secondary patency rates [90, 91]. Jennings et al. [92] published a trial, which showed that Venous Window Needle Guide, a subcutaneously placed hemodialysis cannulation device, is safe and effective in facilitating AVF cannulation for patients with an otherwise mature but noncannulatable access. Strozecki et al. described a case report of a 65-year-old female patient who had several hemodialysis sessions by cannulation of dilated collateral abdominal veins with dialysis needles, as an unconventional vascular access for HD in case of central vein occlusion [93]. Humerobasilic and radiocephalic AVF are the two VA types with the most functioning longevity, although in radiocephalic AVF, there is high initial failure rate [94]. It is the preferable VA due to its longevity, low incidence of complications, and easy cannulation [95–97]. In case of failure of radiocephalic AVF creation, the second most preferable VA is brachiocephalic AVF, which comes first in diabetic patients, in whom the inadequacy of vessels for radiocephalic AVF is usually found [98] with a reported 4-year patency of 80% [99]. According to a study of Rondriguez et al., brachiocephalic AVF has a lower survival than radiocephalic. Four years after its creation, just over 50% of the patients have patent AVF and about 30% after 8 years. Failure at first VA increases the risk for following failure, while successful development of the first VA, at about 60% of patients, does not lead to subsequent failure. Diabetes and female gender seem to be risk factors to VA failure [94].
In the USA, AVGs (Figures 10–12) are the most common type of VA that is used for hemodialysis [100]. However, they last less than AVFs and have more complications such as infections and thromboses [70]. Recent technological advances using tissue-engineered AVGs have shown promise for patients receiving hemodialysis and their potential to provide an attractive, viable option for vascular access [101]. Grafts present a second choice of VA when AVF is not possible to be performed because of vascular problems [102]. AVGs have lower risk of nonmaturation in lower time [103]. They can be placed in the forearm, the upper arm and the thigh, when upper-extremity options are exhausted [104] and they can have a straight, curved or loop configuration. Axillary loop arm graft yields acceptable early patency rates in specific patients with vascular problems [105]. Another advantage is that AVGs may offer a large surface for cannulation. Some types of AVGs such as PTFE AVGs can be cannulated immediately after their placement, according to some studies, although it is preferable to wait for about 2 to 3 weeks for the first cannulation [106, 107]. However, the usual time for a functional graft is 2 to 3 weeks in order to reduce the post surgical edema and the perigraft hematoma and seroma [108]. Karatepe et al. [109] presented a novel polycarbonate urethane nanofabric graft, produced by electrospinning technology, which had self-healing features that avoid seroma formation and allow puncturing within 48 hours. It had good 12-month primary and secondary patency rates and substantially lowers infection rates. Early experience with GORE Acuseal is encouraging with patency and bacteremia rates at least comparable to standard polytetrafluoroethylene grafts, permitting cannulation within 24 hours of insertions and line avoidance in the majority of patients [110].
Upper arm AVG.
Looped forearm AVG.
Straight femoral AVG.
TCs (Figures 2 and 3) have higher mortality risk than AVFs or AVGs; thus, they are used when the creation of the latter is not feasible [111]. There are several reasons that lead to the inability for AVF or AVG creation, such as multiple vascular surgeries, which lead to vascular thrombosis, or when patients have severe peripheral vascular disease or very low cardiac output. TCs are more frequently encountered in pediatric and very old patients. They can also be used as a bridge until AVF or AVG maturation [111]. Their use remains very high during the first year of HD care and is associated with high mechanical and infection rates [112]. The incidence of AVFs has been effectively increased since the “fistula first” has been developed [113], although it is accompanied with an increase in TCs, especially those used as a bridge until the maturation of an AVF [100]. Nonetheless, DOPPS shows an increasing use of TCs for the period 1996 to 2006 in many countries [114], which is in accordance with our data of 2011, which showed increased prevalence of TCs in female hemodialysis patients [115]. It is also signified that it is more likely for a patient to have permanent VA (AVF or AVG) than TC if he is at a center with experienced vascular surgery department successfully creating permanent VA in diabetic, older women and early AVF cannulation practice (within 4 weeks from its formation) [114].
They do not last as much as the others types of VA, and they have higher complication rates such as infections. There are studies revealing that CVCs are colonized within the first 10 days of placement; however, the catheter’s lumen colonization does not equal to positive blood cultures or clinical signs of bacteremia [116]. The guide-wire change or the complete removal of catheter does not affect the outcome of the infection treatment [117]. Power et al. [118] with their study of 759 TCs showed that the appropriate management of catheters can give functional and complication results similar to AVGs. In their study, survival rates were 85%, 72%, and 48% at 1, 2, and 5 years, respectively, while the infection rate was 0.34 per 1000 catheter-days. Although earlier studies showed a lower risk of catheter-related bloodstream infections with internal jugular TCs compared to femoral, recent studies show no difference between the three sites [119, 120].
Transhepatic hemodialysis catheters seem to be a viable alternative option with low morbidity rates [121]. Another safe and effective long-term access is translumbar inferior vena cava [122]. Retrograde femoral vein catheter insertion is a newly applied lifesaving HD vascular access approach for selected ESRD patients with no available HD vascular access at the ordinary sites with accepted HD adequacy, but it needs more evaluation and studies [123].
Renal replacement treatment in children varies. According to North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry of patients reaching ESRD in pediatric centers, 25% submitted preemptive renal transplantation, 50% joined in peritoneal dialysis, and 25% started hemodialysis [124, 125]. The preferable therapy is transplantation and in perspective of a rather short time on HD, children receive maintenance HD through an indwelling CVC [126]. In the USA, no more than 800 pediatric patients receive maintenance HD therapy, while the majority of smaller patients, less than 10 kg or 2 years old, receive peritoneal dialysis [127–129].
However, hemodialysis can be performed successfully in infants and very young children, as well [130]. An evaluation of the vasculature of children who will undergo hemodialysis will indicate the appropriate vascular access. Because of the size of their vessels, there is limited use of AVF in children, although there is an effort to make nephrology society to consider AVF as the best access in pediatric HD patients [131]. According to a 2008 pediatric registry (NAPRTCS) annual report, vascular access for hemodialysis included external percutaneous catheter in 78% of patients, internal AV fistula in 12%, and internal and external AV shunt in 7.3 and 0.7%, respectively [125]. K/DOQI has encouraged greater use of AV fistulas in larger children receiving hemodialysis who are not likely to receive a transplant within 12 months, with a goal of achieving more effective dialysis with fewer complications than the ones occurring with catheters. Patient’s size determines catheter size. An 8-F dual lumen catheter is well tolerated in 4- to 5-kg children, and as the child’s size increases, a vascular access of larger volume can be placed [132]. Blood flow in pediatric patients varies due to the catheter size, which depends on the child’s size. In most of the patients, a recommended blood flow of 3 to 5 ml/kg/min is acceptable [133], providing adequate dialysis with Kt/V equal or greater than 1.2. A recent study by Fadel et al. found a significant correlation between serum soluble vascular cell adhesion molecule 1 and ESA doses in thrombosed AVF, and this could have clinical significance after further investigation [134].
Studies have shown a mortality risk dependent on access type, with the highest risk associated with central venous dialysis catheters, followed by AVGs and then AVFs [135–137]. Recently Hicks et al. [137] stated that this benefit of AVG over TCs may not apply to younger (18–48 years) or older (over 89 years) age-groups. Additionally, patients who had a catheter as the first VA had more complications and higher mortality [138]. The same results have been presented by Ng et al. [139], who examined hospitalization burden related to VA type among 2635 incident patients. The risk for vascular access complications is increased in intensive HD, with overall reported rates being lower in patients with AVF [140]. The CHOICE study examined mortality based on access type in 616 hemodialysis patients for up to 3 years of follow-up. Increased mortality was observed in CVCs and AVGs compared to AVFs in a rate of 50% and 26%, respectively, with greater prevalence in male and elderly patients [141, 142]. Despite these findings and the KDOQI recommendations, dialysis access data from 2002 to 2003 showed that only 33% of prevalent hemodialysis patients in the USA were being dialyzed via AVFs. On the contrary, in Europe and Canada, the majority of the patients [74% and 53%, respectively) were being dialyzed via AVFs [143], but a decreasing trend in the use of AVF seems to take place accompanied by an increasing trend in the use of TCs at the start and after the start of HD [144].
Vascular access admissions continue to fall, with more procedures now performed in an outpatient setting, and are 45% below than in 1993. Among African American patients, the relative risk of an all-cause hospitalization or one related to infection is almost equal to that of Caucasians; the risk of a vascular access hospitalization, however, is 24% higher [145]. Thrombotic occlusion remains a major event, leading to permanent failure in 10% of AVFs and 20% of grafts each year. Interventional (percutaneous transluminal angioplasty and/or stent implantation) or surgical revision of thrombosed accesses has similar outcomes with a high rate of reinterventions. Diabetic elderly patients suffering from peripheral arteriosclerotic obstructive disease are particularly prone to angioaccess-induced hand ischemia [146]. Patients with TCs and AVGs have higher chronic inflammation levels than those with AVFs and increased requirements in epoetin [147]. In our previous work with 149 hemodialysis patients with 202 vascular access procedures (177 Cimino-Brescia AVFs and 25 PTFE AVGs), Cimino–Brescia fistula was used in all patients as the first choice vascular access, except for one patient in the elderly group. Fifteen patients in the elderly group and 7 younger than 65 years old had PTFE AVGs as the third or second choice of VA, respectively. Vascular thrombosis was the only reason of technique failure in both groups. Other complications were aneurysms (10/48 and 14/101), infections (0/48 and 2/101) and edema (0/48 and 6/101) (Table 1). AVF had a 5-year technique survival in two groups of 35% and 45%, respectively (Figure 13). According to our findings, there was no difference in VA complications across age-groups and the first AVF survival was independent of age [6]. Swindlehurst et al. [148] have published similar results, according to which the creation of AVF in the elderly is not only possible but also proved to have a short hospital stay, high patency rates, and an acceptable rate of further intervention. The outcome of AVF benefits more from acknowledging individual vascular conditions rather than age of the patient and therefore AVF creation should not be denied to elderly patients [149]. Among patients over 80 years of age, the AVF as vascular access for HD at the time of dialysis initiation was among the factors that benefit their survival [150].
Cumulative survival of first VA according to the patients’ age.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Thrombosis | \n\t\t\t14/48 | \n\t\t\t39/101 | \n\t\t\tN.S. | \n\t\t
Aneurysm | \n\t\t\t10/48 | \n\t\t\t14/101 | \n\t\t\tN.S. | \n\t\t
Edema | \n\t\t\t0/48 | \n\t\t\t6/101 | \n\t\t\tN.S. | \n\t\t
Infection | \n\t\t\t0/48 | \n\t\t\t2/101 | \n\t\t\tN.S. | \n\t\t
Complications of vascular access
According to the 2010 USRDS Annual Data Report, in 2008, hospitalizations increased, to a point of 46% over 1993. Women on hemodialysis were 16% more likely to be hospitalized than men, overall, in 2007–2008. Also, they had a greater risk than men of cardiovascular, infectious and vascular access hospitalizations 11%, 14%, and 29%, respectively. Recently, in a retrospective single-center analysis, our data varies to those we published in 1998. In 145 patients on HD, we found that female had more possibilities to start HD with double lumen catheter than male and also patients with heart failure independent of gender [115]. Patibandla et al. [151] in their logistic regression model found that increasing age, female sex, black race, lower body mass index, urban location, certain comorbidities and shorter pre-end-stage renal disease nephrology care are all associated with a significantly lower like hood of AVF placement as initial access predialysis. Additionally, there are geographic disparities in AVF creation with decreased rates of AVF placement as the first access in metropolitan, but not rural, populations compared with micropolitan communities [152]. Improvement in standardization of care according to practice guidelines is necessary. AVF rate could be increased by improving access to surgical resources and patients education [153]. Enhancing patient self-care abilities and working together with patients on proper vascular access care can prolong vascular access site viability [154]. Intraoperative blood flow measurements greater than 120 ml/min in AVF and less than 320 ml/min in AVGs may be predictive factors of early failure and fistulography is essential to access patency [155]. In addition to the clinical examination, there are numerous radiological assessments of vascular access pre- and postoperative that enrich our diagnostic armamentarium [156]. Recently, Remuzzi and Manini [157] presented a numerical model that in the clinical setting should allow to reduce the incidence of AVF nonmaturation as well as incidence of VA complications. Cannulation of VA is a crucial part of its management in HD patients and the proper use of the rotating site technique might still be the best approach to cannulation [158]. Evidence do not support the preferential use of buttonhole over rope-ladder cannulation [159]. However, according to systematic review of Muir et al. [160], buttonhole cannulation is associated with higher rates of infectious events, staff support requirements and no reduction in surgical AVF interventions compared with rope ladder in home HD patients.
The nontunneled double lumen catheters’ complications concern the early ones during the insertion and the late ones such as infection and thrombosis of the vessels.
The severity of acute complications varies with the site of insertion. The lowest rate is in the femoral position. A significant complication is perforation of the femoral artery. Bleeding usually resolves within minutes of direct compression and large femoral or retroperitoneal hematomas occur occasionally [161]. Subclavian insertion complications are more serious. The overinsertion of guide wire can occasionally lead to atrial or ventricular arrhythmias, but they are frequently transient [162]. The penetration or cannulation of the subclavian artery can lead to hemothorax, which may require a thoracotomy tube. The incidence of pneumothorax varies from less than 1% to more than 10% of insertions, depending on the skill and experience of the physician. Pericardial rupture and tamponade also have been described [163, 164]. There is less likelihood of arterial puncture or pneumothorax in ultrasound-guided catheter insertion [165]. Subclavian insertion from the left has an increased risk of pneumothorax and atrial perforation, which can be presented with acute hemopericardium upon initiation of dialysis. Internal jugular vein is the preferred site of insertion because of subclavian stenosis and loss of the ipsilateral arm for future hemodialysis access. This complication appears to occur more often with subclavian (40–50%) than with internal jugular insertions (up to 10%) [166, 167]. At internal jugular insertions, a carotid artery penetration may occur, but there is also a lower risk of pneumothorax (0.1%). Post procedural chest X-ray is taken for confirmation of position of catheter tip and to detect early complications, but delayed complications can occur after catheterization. Thus, the patient should be monitored carefully and managed appropriately according to the presenting signs and symptoms [168].
Prevention and treatment of catheter thrombosis are important clinical issues. To prevent formation of thrombus, both lumens of the double lumen catheter are instilled with heparin following hemodialysis [46]. Lytic agents such as urokinase and alteplase are effective in treatment of catheter thrombosis. Alteplase has effectiveness rates in thrombosis treatment comparable to the ones observed with urokinase [169]. Central vein catheters are associated with the development of central vein stenosis [170]. The K/DOQI guidelines therefore recommend avoiding placement in the subclavian vein, unless no other options are available. If central venous thrombosis is detected early, it responds well to directly applied thrombolytic therapy [170] or to percutaneous transluminal angioplasty when the fibrotic stenosis can be crossed with a guide wire [171]. The infection risks associated with temporary double lumen catheters include local exit site infection and systemic bacteremia, both of which require prompt removal of the catheter and appropriate intravenous antibiotic therapy [48, 172, 173]. Bacteremia generally results from either contamination of the catheter lumen or migration of bacteria from the skin through the entry site, down the hemodialysis catheter into the blood stream [174–176]. It seems that prevention strategies should target the first 6 months after access placement or a remedial access-related procedure as over time the risk decline [177]. Skin flora,
There is conflicting evidence concerning the risk of infection based on the site of insertion [172, 182, 183]. Coagulase-negative staphylococci,
Overall, compared with the subclavian vein, the internal jugular vein remains the preferred access site in ambulatory patients. In the intensive care unit, either femoral or internal jugular vein placement is satisfactory, with the use of ultrasound making internal jugular vein placement safer.
The best solution is to prevent the infection by proper placement technique, optimal exit site care and management of the catheter within the HD facility [46, 185]. It is generally believed that CVC can adversely affect permanent VA ipsilateral placement outcomes due to central vein stenosis that they cause, but it seems that the primary failure rate of AVF and AVG is not affected by the presence of an ipsilateral catheter, but cumulative access survival is inferior [186].
Early causes include inflow problems due to small or atherosclerotic arteries, or juxta-anastomotic stenosis, so a preoperative evaluation for suitable access sites has to be performed [187]. Selective use of duplex ultrasonography appears to enhance AVF success rate, although agreed vessels criteria are needed [188]. It seems that the type of anesthesia plays a role in the fistula surgery, with regional anesthesia having a beneficial sympathectomy like effect that causes vasodilation with increased blood flow during surgery and in the AVF postoperatively that may prevent early thrombosis and potentially improve outcome [189], but more evidence are expected to establish this [190].
The etiology of this acquired lesion is not entirely clear but may be related to manipulating the free end of the vein, torsion, poor angulation or loss of the vasa vasorum during anatomic dissection. More often than not, this lesion can be effectively managed with angioplasty [191, 192] or surgical revision [193].
Accessory veins that divert blood flow from the intended superficial vessels to deeper conduits or central venous stenoses due to prior TCs placements may cause outflow problems. Vessels, smaller than one-fourth of the fistula diameter, are usually not hemodynamically relevant. Juxta-anastomotic stenosis and accessory veins are the most common causes for early failure AVFs when preoperative evaluations for suitable access sites have been performed [187]. In elderly population, there is an association of older age, female gender, black race, diabetes, cardiac failure and shorter pre-ESRD nephrology care with predialysis AVF failure [194].
A rather rare complication secondary to bleeding from a catheter-related puncture of an AVF is an acute forearm compartment syndrome [195].
Venous stenosis, thrombosis and attained arterial lesions like aneurysms or stenoses constitute late causes of AVFs’ failure.
As blood flow decreases due to venous stenosis, weekly Kt/V ([dialyzer clearance time]/body volume) decreases and/or recirculation increases, constituting great clinical signs of VA dysfunction. AVF salvage surgery is of paramount importance in order to increase the patency rate, which prolongs survival and increases the patient’s quality of life [196]. Balloon angioplasty followed with stenting maintains the vessel lumen shape over time, as the stent is likely to reduce the risk of restenosis that can otherwise occur after balloon angioplasty because of the viscoelastic recoil of the vessel [197]. According to Aftab et al. [198], for AVF stenosis resistant to conventional percutaneous transluminal angioplasty (PTA), cutting balloon angioplasty may be a better second line treatment given its superior patency rates. It seems that the deficiency of circulating endothelial progenitor cells is associated with early and frequent restenosis after angioplasty of HD VA [199].
Native fistulas will not typically thrombose until flow is severely diminished. The thrombectomy of fistulas, although technically more challenging than in AVGs, is often successful and if flow is reestablished, primary patency is longer than in grafts [200]. Antiplatelet treatment protects fistula from thrombosis or loss of patency but has little or no effect on graft patency and uncertain effects on vascular access maturation for dialysis and major bleeding [201]. Elective repair of subclinical stenosis in AVFs with blood flow >500 ml/min cost-effectively reduces the risk of thrombosis and access loss [202]. Reconstructing the AVF by surgically removing venous neointimal hyperplasia is an effective technique for late hemodialysis access failure which preserves patients’ vessels [203].
As AVF’s size increases over time with increased blood flow, aneurysms may be formed, constituting rather a cosmetic than functional concern, unless stenotic lesions accompany them. If the overlying skin is atrophic or blanching, or there are signs of ulceration or bleeding, a surgical evaluation must be performed urgently [204]. Also, if there is a high association of venous outflow stenosis and AVF aneurysms, comprehensive therapy should encompass treatment of any venous outflow stenosis before open AVF aneurysm repair. A two-stage repair may decrease tunneled HD catheter use in patients with multiple aneurysms [205]. In order to maintain an autogenous access while conserving future dialysis sites, partial aneurysmectomy is recommended as a first-line choice for managing aneurysm associated complications [206]. Also, autologous surgical reconstruction is feasible in the majority of AVF aneurysms. It preserves fistula function and keeps the advantages of an autogenous access [207]. The rupture of such aneurysms in high-flow fistulas can lead to exsanguination and death (Figure 14).
Aneurysm in forearm AVF.
Infections of AVFs are rare but must be treated properly due to patients’ impaired immunologic status. Very rare infections of the AV anastomosis require surgery with resection of the infected tissue. More often, infections occur at cannulation sites and then the arm should be rested and cannulation cease [208]. In all cases of AVF infection, antibiotic therapy is initiated with broad-spectrum vancomycin plus an aminoglycoside and converting to appropriate one based on results of culture and sensitivities. Infections of primary AVFs should be treated for a total of 6 weeks, analogous to subacute bacterial endocarditis [209].
AVGs have a functional life much shorter than AVFs. Neointimal hyperplasia causes venous stenosis, which leads to thrombosis, and this is the natural course of AVGs. The principal cause of thrombosis is the increased production of smooth muscle cells, myofibroblasts and vascularization within the neointima. Around the graft, there is also angiogenesis and numerous macrophages in the tissue [210, 211]. Growth factors (GF) such as VEGF (vascular endothelial), PDGF (platelet derived) and basic FGF (fibroblast) are present within the neointimal lesion [211]. The presence of shear stress regulates vascular endothelium [212, 213] and that flow within AVGs is likely to be different from native veins. Understanding the pathophysiology of neointimal hyperplasia could lead to targeted therapy. Current studies are evaluating the role of radiation [214], decoy peptides against transcription factors [215, 216] and local delivery of drugs with cell-cycle inhibitory effects (e.g., paclitaxel [217] and sirolimus). Cell-based strategies seek to take advantage of endothelial progenitor cells that release endogenous inhibitors of proliferation and thrombosis, such as nitric oxide (NO) and prostacyclin [218]. Venous stenosis in AVGs leads to decreased blood flow and thrombosis, at a rate of 1–1.5 times/patient/year [70]. Thrombosis is associated with anatomical stenosis, in most cases, which is located in the venous anastomosis (60%), followed by the peripheral vein (37%) and within the graft (38%) [219]. Stenosis and closure by venous anastomoses are the most frequent causes of failure of AVG for hemodialysis. AVG closure can be addressed surgically and endovascularly (amenable to thrombectomy by radiological or surgical means) [220]. Percutaneous angioplasty is safe and effective in treating venous stenosis [221], with a success rate of 80% to 94% and primary patency around 60% at 6 months and 40% at 1 year. The placement of self-expanding nitinol stents at the venous anastomosis appears to prolong patency in cases where focal lesions are resistant to repeated angioplasty and recur and improve PTFE grafts longevity in selected cases of older grafts [222]. Central stenosis is technically more difficult to treat, and stenotic lesions often recur within 6 months [77]. Recently, a modular anastomotic valve device (MAVD) has been in preliminary use in order to isolate the graft from the circulation between dialysis sessions, decreasing the flow disturbances this way and as a result the intimal hyperplasia [223]. During the last decades, percutaneous techniques became increasingly important for the treatment of AVG failure [224]. Cutting balloon angioplasty is a safe and effective treatment of graft to vein anastomotic stenosis, with significantly higher patency than that of conventional balloon angioplasty [225]. From the point of view of Troisi et al. [226], the combined simultaneous hybrid (open and endovascular) approach in urgency maximizes the use of different available techniques, improving overall success rate to save a thrombosed graft.
As described above, AVGs’ thromboses are usually the result of multiple factors; such as stenosis, hypotension and excessive compression for hemostasis. Hemodialysis nurses have to be careful in order to avoid these factors. Thrombosis risk increases as blood flow (BF) decreases, as May et al. [227] showed in their study. AVG thrombosis can be managed in an outpatients’ basis endovascularly. Angiography for venous stenosis is always required and is often accompanied by an angioplasty.
Prompt pharmaceutical thrombolysis or mechanical removal of the thrombus with a Fogarty catheter and thromboaspiration or thrombectomy with a mechanical device [228] may avoid a new catheter placement.
Infections of AVGs are severe complications and the second cause of vascular access loss. Hemodialysis-related bacteraemia is 10-fold more often in AVGs than AVFs: 2.5 incidents every 1000 HD sessions versus 0.2 [229]. It seems that the most significant modifiable risk factor is patients’ hygiene [230].
A referral to surgeon of pseudoaneurysms for resection is imposed when they are increasing rapidly in size, their width is more than 2-fold bigger than the graft, or the overlying skin seems under duress (thin, bleeding, blanching) [231].
Ischemia, as a result of access placement, is more common for AVGs than AVFs: vascular steal syndrome and ischemic monomelic neuropathy are two important clinical entities to distinguish.
“Physiological” steal phenomenon occurs in 73% of AVFs and 90% of AVGs. Thus, in a radiocephalic fistula, arterial blood from the palmar arch may also deliver blood into the fistula. Unless there is the capacity for collateralization, this can lead to ischemia in the hand, ranging from complaints about cold hands to necrotic fingertips. Most of these complaints improve over time, but 1% of AVFs and up to 4% of AVGs require surgical revision [232]. Doppler ultrasonography is a useful adjunctive tool to determine the etiology of chronic hemodialysis access-induced distal ischemia (HAIDI). Conservative measures combined with close follow-up can be used as the first step in the management of chronic HAIDI patients with mild symptoms [233]. Ischemic monomelic neuropathy is characterized by warm hands with a good pulse, but the hands are tender and swollen, usually immediately after surgery, and there is muscle weakness [234]. The cause is likely ischemia of the nerves, and rapid surgical reevaluation is needed. Wound and skin complications and greater incidence of thrombosis of VA associated with recombinant human erythropoietin have been reported (rHuEPO) [235].
Early or late catheter dysfunctions are the functional complications of TCs. Kinking and unsuitable positioning of the catheter tip may be the cause of early dysfunction and can be managed under fluoroscopic guidance. Around or at the catheter tip, fibrin sheaths and thrombi can be formed constituting late causes of failure. Balloon angioplasty can disrupt fibrinous sheaths, improving flow through a new catheter in the same location. Valliant et al. [236] have demonstrate in their study that there is no significant increase in bacteraemia and subsequent catheter dysfunction rates after fibrin sheath disruption by balloon procedure compared to simple over the wire exchange. Symptomatic occlusions of the central veins usually require the removal of the catheter and system anticoagulation and must be weighed in the context of a continued need for dialysis and other available access options. Yoon et al. recently referred a novel two-stage hemodialysis reliable outflow (HeRO) graft implantation technique that avoids the use of a femoral bridging hemodialysis catheter in internal jugular vein (IJV) catheter-dependent patients with contralateral central venous occlusion and thus lowering the risk of infection related to a femoral catheter [237]. The use of catheter is related to a higher incidence of infection and could compromise dialysis adequacy [238, 239]. Catheter-related infections (CRI) are linked with increased all cause morbidity and mortality. The 8–10% of MRSA bacteraemia in the UK occurs in patients receiving long-term hemodialysis. It appears that the catheter locking with appropriate antimicrobial lock solutions (ALS) decrease the infections’ incidence in HD patients [180, 240, 241]. It seems that prophylaxis with gentamicin of the catheter lumens reduces bacterial infection morbidity and mortality-related bacteremia of catheter without obvious bacterial resistance, making such use advisable [242]. Even taurolidine–citrate–heparin catheter lock solution reduces staphylococcal bacteraemia rates in HD patients [243] and improves the inflammatory profile in HD patients with TCs [244]. Del Pozo et al. [245] in their prospective study showed that an evaluation of tunneled catheters with intracatheter leukocyte culture helps in the early colonization of HD catheters, giving the possibility to eradicate biofilm without the removal of catheter. Recent studies have demonstrate that the “shower and no-dressing” technique appears to be a safe TC option that improves quality of life [246, 247], although there is skepticism and uncertainty about the appropriate dressing [248].
Unfortunately, there are no revolutionary changes in the field of vascular access for hemodialysis in the last years. According to the guidelines, AVFs are still the best choice. Luckily, AVGs’ survival has been increased, but still TCs are used in a great portion of ESDRD patients.
As a result, humerobasilic and radiocephalic AVFs are the two VA types with the most functioning longevity. However, AVFs’ primary patency rates at 1 year vary considerably between USA and Europe. Hemodialysis patients with AVF seem to have lower mortality.
The incidence of AVFs has been effectively increased since the “fistula first” has been developed, although it is accompanied with an increase in TCs.
AVGs as a second choice remain a good solution for patients without the possibility of AVF and the survival of grafts has been improved.
TCs seem to be a new reality in most American and European dialysis units because of the increase of number of elderly patients and with heart failure. Early referral to nephrologists and patient’s education has an important role for a successful VA.
Additionally, the cannulation of VA is a crucial part of its management in HD patients and the proper use may improve the survival of VA.
Summarized from the international literature and our experience, when there are suitable vessels, the creation of AVF is of top priority. When this is not feasible or there is an AVF failure, AVGs or TCs are the first choice alternative or the second best, respectively. Female and old patients are more likely to initiate HD treatments via TC. A well-matured and functioning permanent vascular access is of great importance for its longevity and thus early referral to a nephrologist is mandatory.
Bacteria, fungi (yeasts and molds), mycobacteria, prions, protozoa, and viruses are common pathogens infecting humans and animals. They typically exist within the host or in the environment. It has been observed that these microorganisms exhibit a notable difference in the natural survivability in the environment, as well as susceptibility to chemical and physical inactivation. For example, under ambient and dried conditions, human coronaviruses seem to lose their infectivity in a matter of several hours to several days [1], whereas endospores and prions may remain infectious for years to decades or even indefinitely [2, 3].
As more and more data have become available regarding the survivability and susceptibility of pathogens to microbicides, it has been observed that the pathogens seem to demonstrate an order of susceptibility to chemical and physical inactivation. E. H. Spaulding first proposed a classification system for the sterilization and disinfection of medical instruments based on the infection risk in 1939 [4]. On the basis of this classification, the concept of a hierarchy of pathogen susceptibility was proposed, in which microorganisms are placed into several groups and ranked from least susceptible to most susceptible. In this hierarchy concept, bacterial spores were ranked the least susceptible, followed by mycobacteria, non-enveloped viruses, fungi, vegetative bacteria, and enveloped viruses. The susceptibility hierarchy was also believed to be related to the biochemical and biophysical characteristics of a pathogen [5, 6].
This hierarchy concept has been slightly modified and expanded over the years. For example, prions were added and considered less susceptible to inactivation by microbicides than bacterial spores; small non-enveloped viruses were considered less susceptible than large non-enveloped viruses; and the order between mycobacteria and small non-enveloped viruses was sometimes reversed (Figure 1) [7, 8, 9, 10]. Additionally, it has been suggested that the hierarchy concept may be applied either “vertically” (i.e., ranking of susceptibility
Proposed hierarchy of susceptibility of pathogens to microbicides. Note: slightly different versions of the hierarchy concept have been proposed in the literature. Mycobacteria have been placed above small non-enveloped viruses, and molds have been placed above large non-enveloped viruses in certain versions. In some versions, the small and large non-enveloped viruses are combined; and yeasts and molds may be combined.
The hierarchy concept has been quite useful for enabling scientists to better understand the innate difference among various types of pathogens. In the case of newly emerged pathogens, especially, the hierarchy concept has helped stakeholders design and implement a disinfection strategy swiftly with a reasonable level of confidence. The concept also helps the contaminant control for food, pharmaceutical, and biopharmaceutical products, as it is impractical to test every possible contaminating pathogen, and a robust infectivity assay system may be lacking for certain pathogens (e.g., hepatitis E virus).
Despite its usefulness, the hierarchy concept should be interpreted with caution, as it may oversimply the differences and trending of pathogen susceptibilities. Further examination and refinement of the concept may be necessary; and several important questions should be answered. For example, how often do exceptions to the hierarchy occur and what are the underlying reasons? Could a trending be specific to a given type of chemistry? Is the hierarchy the same between susceptibility to both chemical and physical inactivation? Why do pathogens in the same group, or even the same family or genus, sometimes exhibit striking differences in susceptibility? Is there a way to identify and separate reliable/consistent trending versus blurred/variable trending? A deeper look at the efficacy data for various types of microbicidal actives, especially for non-enveloped viruses, may help stakeholders understand the scope, reliability, and limitation of the hierarchy concept so that it can be best utilized.
This chapter reviews the inactivation efficacy data from the literature against non-enveloped viruses for several commonly used types of chemistries, either in formulated or unformulated form, in an effort to generate a separate relative order of susceptibility among these non-enveloped viruses for each type of chemistry and to differentiate consistent versus variable trending. Physical inactivation approaches are not covered in this chapter, although a significant degree of variation also exists for physical treatments. It is not clear that the physical inactivation approaches, in general, are governed by the same hierarchy to susceptibility as is observed for chemical inactivation approaches [12].
Currently, there are a total of 21 families of viruses (including enveloped and non-enveloped) identified for humans [13], which represent only a small part of the entire paradigm of viruses in nature, whose host ranges extend from vertebrates to plants to bacteria. The most common families of non-enveloped viruses for humans and animals include
Family | Example virus | Abbreviation | Genus | Genome | Size (nm) |
---|---|---|---|---|---|
Adenovirus type 2 | AdV-2 | ds DNA | 70–90 | ||
Adenovirus type 5 | AdV-5 | ds DNA | 70–90 | ||
Adenovirus type 8 | AdV-8 | ds DNA | 70–90 | ||
Human astrovirus | HAstV | ss RNA | 28–35 | ||
Feline calicivirus | FCV | ss RNA | 28–40 | ||
Human norovirus | HuNoV | ss RNA | 28–40 | ||
Murine norovirus | MNV | ss RNA | 28–40 | ||
Tulane virus | TuV | ss RNA | 28–40 | ||
Porcine circovirus | PCV | ss DNA | ∼17 | ||
Hepatitis E virus | HEV | ss DNA | 32–34 | ||
Human papillomavirus | HPV | ds DNA | 50–60 | ||
Bovine parvovirus | BPV | ss DNA | 20–28 | ||
Canine parvovirus | CPV | ss DNA | 20–25 | ||
Human parvovirus B19 | B19V | ss DNA | 23–26 | ||
Minute virus of mice | MVM (MMV) | ss DNA | 20–25 | ||
Porcine parvovirus | PPV | ss DNA | 20–25 | ||
Bovine enterovirus | BEV | ss RNA | 30–32 | ||
Coxsackievirus | Cox | ss RNA | 30–32 | ||
Echovirus 11 | Echo11 | ss RNA | 30–32 | ||
Encephalomyocarditis virus | EMCV | ss RNA | 30–32 | ||
Enterovirus 71 | EV-71 | ss RNA | 30–32 | ||
Enterovirus D68 | EV-D68 | ss RNA | 30–32 | ||
Foot and mouth disease virus | FMDV | ss RNA | 30–32 | ||
Hepatitis A virus | HAV | ss RNA | 30–32 | ||
Poliovirus type 1 | PV1 | ss RNA | 30–32 | ||
Rhinovirus | RV | ss RNA | 30–32 | ||
Seneca Valley virus | SVV | ss RNA | 30–32 | ||
Bovine polyomavirus | BPyV | ds DNA | 40–50 | ||
Simian virus 40 | SV40 | ds DNA | 40–50 | ||
Bluetongue virus | BTV | ds RNA | 60–80 | ||
Reovirus type 3 | REO-3 | ds RNA | 60–80 | ||
Rotavirus | Rota | ds RNA | 60–80 |
Common families of human and animal non-enveloped viruses.
Among these, the
It is worth noting that viruses are typically classified taxonomically on the basis of virion properties (size, shape, envelope, physical, and chemical properties, etc.), genome organization, replication mechanism, antigenic properties, and biological properties [13, 14, 15]. The final classification is a combined consideration of these properties. However, the stability and susceptibility to inactivation of a virus may not relate to all of these properties and, as such, may not always align with the taxonomic classification system. For example, the susceptibility of a virus to surfactants may primarily be related to the envelope of the virion and not related to the genome structure or mode of replication.
The susceptibilities of non-enveloped viruses to chemicals have been found to be highly variable and somewhat hard to predict, since they do not always agree with the hierarchy concept. For example, according to the hierarchy concept as modified by Sattar [8], small non-enveloped viruses should be less susceptible than large non-enveloped viruses. Additionally, if there is a fixed hierarchy, all small non-enveloped viruses should either display similar levels of susceptibility or should demonstrate a definitive trend of relative susceptibility, regardless of the type of microbicide. Based on the literature, neither of these predictions appear to hold in every case. The relative order of susceptibility seems chemistry-dependent; and sometimes viruses within the same family or even genus have been found to exhibit unequivocal differences in their susceptibilities (reviewed in [16]). Any trending or hierarchy, therefore, must be reviewed in the context of the type of chemistry, and it should not be assumed that non-enveloped viruses within the same family or genus will always display similar susceptibilities to a given microbicide.
Viral inactivation may be achieved by chemical and/or physical methods. The subset of chemicals commonly used for inactivation of non-enveloped viruses includes alcohols, oxidizers, halogen compounds, quaternary ammonium compounds, phenolics, aldehydes, acids, and alkalines [17, 18, 19]. These differ with respect to efficacy, stability, toxicity, material or surface compatibility, cost, and sensitivity to organic soil load. Soil load is a term used to signify an organic matrix used to challenge the inactivating efficacy of a microbicide. It is intended to mimic secretions or excretions in which the virus would be released from an infected person or animal. Some chemistries (e.g., sodium hypochlorite, phenolics, and aldehydes) are mostly used for environmental or medical device disinfection. Other chemistries (e.g., ethanol) are more commonly used for hand hygiene, while some others (e.g., quaternary ammonium compounds) may be used for both environmental disinfection and skin antisepsis (Table 2).
Class | Chemical | Typical conc. | Usage | Mechanism of viral inactivation | Sensitivity to soil load |
---|---|---|---|---|---|
Alcohols | Ethanol | 50–95% | Disinfection; Antisepsis | Protein denaturation | + |
Isopropanol | 70–90% | Disinfection | Protein denaturation | + | |
Oxidizers | Sodium hypochlorite | 0.01–0.5% | Disinfection | Protein/genome damage | ++ |
Chlorine dioxide | 0.1–1 mg/L | Disinfection; Water treatment | Protein/genome damage | — | |
Hydrogen peroxide | 0.1–10% | Disinfection; Antisepsis | Lipid/protein/genome damage | + | |
Hypochlorous acid | 0.002–0.1% | Disinfection; Water treatment | Protein/genome damage | ++ | |
Peracetic acid | 0.01–1% | Disinfection; Sterilization | Protein denaturation | — | |
Povidone-iodine | 0.02–8% | Disinfection; Antisepsis | Protein/genome damage | ++ | |
Chlorohexidine | 0.02–0.2% | Antisepsis | Protein denaturation | + | |
QAC | BKC, DDAC, etc. | 0.01–0.2% | Disinfection | Lipid/protein damage | + |
Low pH | Acids | ≤ pH 4 | Sanitization; Biomanufacturing | Capsid/protein damage | — |
High pH | NaOH, etc. | ≥ pH 10 | Disinfection; Tissue processing | Capsid/genome damage | — |
Aldehydes | Glutaraldehyde | 0.02–2% | HLD; Sterilization | Crosslinking/protein & genome damage | — |
Formaldehyde | 0.1–5% | Disinfection/Preservation | Alkylating/protein & genome damage | — | |
OPA | 0.02–2% | HLD; Sterilization | Crosslinking/protein damage | — | |
Phenolics | Phenylphenol, etc. | 0.05–5% | Disinfection | Protein damage | — |
Common types of chemistries used for non-enveloped viral inactivation.
Abbreviations used: BKC, benzalkonium chloride; Conc, concentration; DDAC, didecyldimethylammonium chloride; HLD, high-level disinfection; NaOH, sodium hydroxide; OPA, ortho-phthaldehyde; QAC, quaternary ammonium compounds.
The virucidal efficacy of a product is not only determined by the type and concentration of the chemical, but is also heavily influenced by the formulation, pH, exposure (contact or dwell) time, organic soil load, temperature, and surface characteristics (as applicable), etc. [10, 20, 21, 22]. Given the differences between various testing methods, as well as the intrinsic variability of viral infectivity (titration) assays, a general conclusion on the efficacy of a particular type of active ingredient will be enhanced if the efficacy is derived from multiple sets of data and under various application conditions (such as the concentration of the microbicidal active(s), contact time, formulation matrix (as applicable), and organic soil load, etc.) Additionally, in order best to explore the relative ranking of susceptibility between viruses, or the lack thereof, efficacy data from side-by-side studies wherein the same test methodologies and conditions were used would be preferable. Care should be taken when comparing data from different studies, especially if the formulations, test methods, and test conditions were different.
Alcohols, primarily ethanol and isopropanol, are widely used for hand hygiene and environmental disinfection, and their efficacies against bacteria and viruses have been extensively studied [23, 24, 25]. Ethanol at a concentration of 70–90% and isopropanol at 70% have been broadly shown to be effective against enveloped viruses; however, their efficacies against non-enveloped viruses are much more variable.
The trending of the degree of susceptibility of non-enveloped viruses to ethanol and isopropanol is generally clearer and more consistent than it is for many other types of chemistries, thanks to the large amount of data in the literature. The relative ranking of susceptibility of non-enveloped viruses seems to differ between ethanol and isopropanol; and the ranking does not appear to align well with the classical virological taxonomy.
For ethanol, parvoviruses and the polyomavirus simian virus 40 have low susceptibility, while rotavirus (a reovirus) is susceptible (Table 3). Viruses in the
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
30 s | 1 min | 5 min | 10 min | ||||
PPV | Stainless steel | Erythrocytes + BSA | 0.3 | 0.6 | [26] | ||
MVM | Stainless steel | Erythrocytes + BSA | 0.3 | 0.7 | [26] | ||
HEV71 | Suspension test | Medium | < 1 | [27] | |||
HAV | Suspension test | Medium | 0.4 | [28] | |||
HAV | Suspension test | 20% fecal | 0.4 | [28] | |||
HuNoV | Suspension test | 20% stool | <0.5 | [29] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PV1 | Suspension test | 20% fecal | 0.3 | [28] | |||
PV1 | Suspension test | Medium | 0.4 | [31] | |||
PV1 | Glass | Medium | 2.3 | 1.0 | 5.0 | [31] | |
PV1 | Stainless steel | Erythrocytes + BSA | 2.1 | 1.8 | [26] | ||
PV1 | Suspension test | Medium | 4 | [28] | |||
FCV | Suspension test | Medium | 1.7 | 2.2 | [30] | ||
AdV-8 | Suspension test | Medium | 1.9 | [33] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 2.4 | >4.1 | [26] | ||
AdV-5 | Stainless steel | Medium | ∼5 | [34] | |||
MNV | Suspension test | Medium | 5 | [30] | |||
Rotavirus | Suspension test | Medium | > 3.1 | [28] | |||
CPV | Stainless steel | Medium | 0.1 | [36] | |||
SV40 | Suspension test | Medium | <1 | [37] | |||
PV1 | Glass | Medium | 2.9 | 2.9 | 5.4 | [31] | |
TuV | Suspension test | Medium | <0.5 | [30] | |||
FCV | Suspension test | Medium | <0.5 | [30] | |||
HEV71 | Suspension test | Medium | <1 | [27] | |||
PV1 | Suspension test | medium | <1 | [37] | |||
PV1 | Glass | Medium | 1.2 | 1.3 | 1.0 | [31] | |
AdV-5 | Stainless steel | Medium | ∼1 | [34] | |||
AdV-8 | Suspension test | Medium | 2.0 | [33] | |||
MNV | Suspension test | Medium | 1.8 | 3.1 | [30] | ||
SV40 | Suspension test | Medium | >4 | [37] | |||
Rotavirus | Suspension test | Medium | > 4 | [42] |
Efficacy of alcohols against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; RT, room temperature.
Entries in purple font indicate results from undiluted or diluted formulations with the indicated microbicidal active ingredients.
Interestingly, the above order of susceptibility does not appear to hold the same for isopropanol (Table 3). For example, the polyomavirus simian virus 40 is much more susceptible to isopropanol than many other non-enveloped viruses; and poliovirus appears to display a lower susceptibility, similar to that of hepatitis A virus and human enterovirus 71. Murine norovirus is still more susceptible than feline calicivirus to isopropanol, but not as susceptible as simian virus 40 or rotavirus. The apparent difference between adenovirus 5 and adenovirus 8 that has been observed for ethanol has not been observed for isopropanol.
An oxidizer or oxidizing agent is a chemical that has the ability to oxidize other molecules, i.e., to accept their electrons. Common oxidizing agents used for disinfection, sterilization, or antisepsis include hydrogen peroxide, peracetic acid, ozone, and halogen-containing compounds such as sodium hypochlorite (bleach), hypochlorous acid, povidone-iodine, chlorohexidine, and chlorine dioxide, etc. These compounds can react with and alter the proteins and nucleic acids of non-enveloped viruses and render them noninfectious. Oxidizers comprise a large group of chemicals, and the relative order of susceptibility of non-enveloped viruses to oxidizers seems to vary by specific type of active ingredient (Table 4).
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
≤ 1 min | 2 min | 5 min | 10 min | ||||
FCV | Suspension test | Medium | 3 | [29] | |||
FCV | Suspension test | 20% stool | 0.5 | [29] | |||
MNV | Suspension test | Medium | 3 | [29] | |||
MNV | Suspension test | 20% stool | 0.0 | [29] | |||
CPV | Stainless steel | 90% plasma | < 1 | [43] | |||
CPV | Stainless steel | 5% serum | 5 | [43] | |||
HAV | Stainless steel | 5% serum | 5 | [43] | |||
HAV | Stainless steel | 90% plasma | <1 | 5 | [43] | ||
HAV | Suspension test | PBS/20% fecal | 4 | [28] | |||
PV1 | Suspension test | PBS/20% fecal | 4 | [28] | |||
PPV | Stainless steel | Erythrocytes + BSA | 0.6 | 1.0 | [26] | ||
MVM | Stainless steel | Erythrocytes + BSA | 3.0 | 4.4 | [26] | ||
PV1 | Stainless steel | Erythrocytes + BSA | 2.8 | 4.5 | [26] | ||
AdV-5 | Stainless steel | Erythrocytes + BSA | 4 | [26] | |||
PV1 | Glass | Medium | 0.4 | 0.9 | [16] | ||
RV14 | Glass | Medium | >4.9 | [16] | |||
PPV | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | 1.5 | [26] | |||
PV1 | Stainless steel | Erythrocytes + BSA | 3.9 | [26] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 2.3 | [26] | |||
MNV | Suspension test | Medium | ∼3 | [52] | |||
HAV | Suspension test | Medium | ∼3 | [53] | |||
PV | Suspension test | Medium | >3 | [53] | |||
CPV | Stainless steel | BSA | 1.6 | [34] | |||
MVM | Stainless steel | BSA | 2.3-2.9 | [34] | |||
PPV | Stainless steel | BSA | 3.8-5.5 | [34] | |||
AdV-5 | Stainless steel | BSA | 4.9-5.8 | [34] |
Efficacy of oxidizers against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; PBS, phosphate buffered saline; medium, culture medium; RT, room temperature.
Viral-inoculated lettuce was washed with PAA solution for a defined period of time.
Entries in purple font indicate results from undiluted original or diluted formulations with microbicidal active ingredients.
Parvoviruses are generally among the least susceptible viruses to various types of oxidizers, including sodium hypochlorite, hydrogen peroxide, and peracetic acid. However, for sodium hypochlorite, minute virus of mice appears to be more susceptible than porcine parvovirus and canine parvovirus. All picornaviruses appear to exhibit a similar degree of susceptibility to sodium hypochlorite; but within the family of
The trending for hydrogen peroxide seems more complex than that for sodium hypochlorite. For example, there seems a higher level of variability within the
For peracetic acid, hepatitis A virus also seems less susceptible than poliovirus. Both feline calicivirus and murine norovirus are susceptible to peracetic acid and so is adenovirus.
Quaternary ammonium compounds (QAC) are widely used as active ingredients for disinfectants. Among the advantages of QAC are good stability, dual function of disinfection and cleaning, surface activity, low toxicity, and lack of odor, etc. The potential limitation in the microbicidal efficacy and possible effect in promoting antimicrobial resistance of QAC have also been discussed in the literature [54, 55].
Quaternary ammonium compounds are generally efficacious on most vegetative bacteria and enveloped viruses. Their efficacies against non-enveloped viruses, however, are generally much weaker. Nevertheless, several non-enveloped viruses, such as rotavirus, rhinovirus, and coxsackievirus A11, have been shown to be susceptible to QAC. The susceptibility levels among the
Virusa | Method | Soil/matrixb | Log10 reduction after | References | |||
---|---|---|---|---|---|---|---|
30 s | 1 min | 10 min | 60 min | ||||
PPV | Stainless steel | Erythrocytes + BSA | 0.4 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
PV1 | Stainless steel | Erythrocytes + BSA | 0.5 | [26] | |||
AdV-5 | Stainless steel | Erythrocytes + BSA | 1.8 | [26] | |||
AdV-8 | Suspension test | Medium | 1.0-1.8 | [57] | |||
AdV-5 | Suspension test | Medium | 3.7-5.3 | [57] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PV1 | Suspension test | BSA/yeast extract | 0.0 | [58] | |||
AdV-25 | Suspension test | BSA/yeast extract | 0.3 | [58] | |||
Cox A11 | Suspension test | BSA/yeast extract | >5.1 | [58] | |||
FCV | Suspension test | Medium | <0.5 | [29] | |||
MNV | Suspension test | Medium | <0.5 | [29] | |||
Rhinovirus | Glass | Medium | >3.0 | >3.3 | [16] |
Efficacy of QAC against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; QAC, quaternary ammonium compound.
Entries in purple font indicate results from original or diluted formulations with microbicidal active ingredients.
Acids and alkalines, either used alone or in combination with other active ingredients in formulated products, can be an effective means for viral inactivation. Acids may be used for disinfection, sanitization, textile or face mask pretreatment, or viral clearance during biopharmaceutical manufacturing. Alkalines may also be used for disinfection, sanitization, and viral clearance during biopharmaceutical manufacturing and can be effective against even the least susceptible of pathogens, the prions [58].
It has been widely reported that a low-pH treatment (typically at pH 4 and below) can effectively inactivate most enveloped viruses, although some enveloped viruses, such as bovine viral diarrhea virus, still exhibit a relatively low susceptibility to this treatment pH [22]. The range of susceptibilities of non-enveloped viruses to low pH seems quite scattered and often goes against the “conventional wisdom” that non-enveloped viruses are not susceptible to acidic pH (Table 6). For instance, in the family of
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
20 min | 30 min | 45 min | 1–2 hr | ||||
REO-3 | Suspension test | Medium | 1–3 | [59] | |||
PCV | Suspension test | Medium | >3 | [60] | |||
MVM | Suspension test | Medium | <1 | [61] | |||
MNV | Suspension test | Medium | <0.5 | [30] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
PARV4 | Suspension test | Medium | 2–3 | [61] | |||
B19V | Suspension test | Medium | > 4 | [61] | |||
FCV | Suspension test | Medium | 6.3 | [30] | |||
FCV | Suspension test | Medium | >5 | [62] | |||
PV | Suspension test | Medium | <1 | [63] | |||
PV | Suspension test | Medium | <1 | [64] | |||
HAV | Suspension test | Medium | <1 | [64] | |||
MNV | Suspension test | Medium | <0.5 | [30] | |||
TuV | Suspension test | Medium | <0.5 | [30] | |||
Cox A9 | Suspension test | Medium | <1 | [65] | |||
FCV | Suspension test | Medium | ∼3 | [30] | |||
FCV | Suspension test | Medium | ∼4.7 | [62] | |||
RV | Suspension test | Medium | >3 | [65] | |||
FMDV | Suspension test | Medium | >3 | [65] | |||
MVM | Suspension test | Medium | <1 | [66] | |||
EV71 | Suspension test | Medium | <1 | [67] | |||
EV-D68 | Suspension test | Medium | ∼4–5 | <5 | [67] | ||
B19V | Suspension test | Medium | [66] |
Efficacy of low pH against non-enveloped viruses.
The
Feline calicivirus and murine norovirus in the family
Viruses, both enveloped and non-enveloped, are generally susceptible to high pH. At an environment of pH 12 or above, most if not all non-enveloped viruses would be inactivated, with extent depending both on temperature and contact time. Reovirus, simian virus 40, hepatitis A virus, canine parvovirus, poliovirus, murine norovirus, and Tulane virus seem to be less susceptible than minute virus of mice, feline calicivirus, adenovirus, rotavirus, and foot-and-mouth disease virus. It may be worth noting that the order of susceptibility to high pH seems to be in discord with the hierarchy concept by the greatest degree: in this case, an enveloped virus, bovine viral diarrhea virus, seems to be less susceptible than most, if not all, non-enveloped viruses [22]; parvoviruses are not necessarily less susceptible than many other non-enveloped viruses; and the size of the viral particle does not seem to matter much with regard to the degree of susceptibility (Table 7).
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
≤ 1 min | 10 min | 30 min | 1 hr | ||||
MNV | Suspension test | Medium | ∼2 | [30] | |||
TuV | Suspension test | Medium | ∼2.2 | [30] | |||
FCV | Suspension test | Medium | >5.5 | [30] | |||
REO-3 | Suspension test | Medium | 3 | [68] | |||
Cox B | Suspension test | Medium | 5 | [69] | |||
Echo 11 | Suspension test | Medium | 6 | [68] | |||
BVDV | Suspension test | Medium | 2.5 | [70] | |||
HAV | Suspension test | Medium | 2.7 | [59] | |||
SV40 | Suspension test | Medium | 3.9 | [70] | |||
HAV | Stainless steel | 5% serum | 3.0 | [43] | |||
HAV | Stainless steel | 90% plasma | 3.6 | [43] | |||
CPV | Stainless steel | 5% serum | 3.5 | [43] | |||
CPV | Stainless steel | 90% plasma | 5.2 | [43] | |||
MVM | Suspension test | Medium | >4.7 | [71] | |||
MVM | Suspension test | Medium | >4 | [66] | |||
CPV | Suspension test | Medium | 5.6 | [70] | |||
PV | Suspension test | Medium | 5.9 | [70] | |||
AdV-2 | Suspension test | Medium | >6.9 | [70] | |||
AdV-5 | Suspension test | Medium | >6 | [72] | |||
HAV | suspension test | Medium | 2.4 | [59] | |||
PV | suspension test | Medium | 4.1 | [63] | |||
Avian Reo | Suspension test | Medium | 4 | [73] | |||
PV | Suspension test | Medium | 5.1 | [73] | |||
Bovine Rota | Suspension test | Medium | >6 | [73] |
Efficacy of high pH against non-enveloped viruses.
Entries in purple font indicate results from undiluted or diluted formulations with microbicidal active ingredients.
Aldehydes, such as glutaraldehyde, formaldehyde, and
Virusa | Method | Soil/Matrixb | Log10 Reduction after | References | |||
---|---|---|---|---|---|---|---|
5 min | 10 min | 30 min | 60 min | ||||
HAV | Suspension test | Medium | 3.0 | [75] | |||
PPV | Stainless steel | BSA | 1.7–2.8 | [34] | |||
MVM | Stainless steel | BSA | 2.5–3.3 | [34] | |||
PV1 | Suspension test | Medium | >3 | [76] | |||
AdV-5 | Stainless steel | BSA | 4.9–6.3 | [34] | |||
PPV | Stainless steel | Erythrocytes + BSA | 3.6 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | >4.4 | [26] | |||
AdV-5 | Suspension test | Medium | >5.0 | [77] | |||
Ortho-phthaldehyde, 0.55% | |||||||
PPV | Stainless steel | Erythrocytes + BSA | 3.6 | [26] | |||
MVM | Stainless steel | Erythrocytes + BSA | >4. | [26] |
Efficacy of aldehydes against non-enveloped viruses.
See Table 1 for abbreviations used for viruses.
BSA, bovine serum albumin; medium, culture medium; RT, room temperature.
Entries in purple font indicate results from original or diluted formulations with microbicidal active ingredients.
In the simplified hierarchy of susceptibility of pathogens to microbicides concept, small non-enveloped viruses are considered less susceptible than large non-enveloped viruses, and both groups of non-enveloped viruses are believed to be less susceptible than enveloped viruses. The hierarchy concept also assumes that the ranking applies to all types of microbicidal actives. Additionally, the hierarchy concept can generally lead to common notions that viruses that share similar virological properties (e.g., same family or genus of virus) may be expected to display similar degrees of susceptibility and that the smaller a virus is, the less susceptible it will be to microbicides in general.
These generalizations are correct, to a degree. For example, most enveloped viruses are indeed more susceptible than non-enveloped viruses to chemical inactivation. It should be noted though that exceptions to the hierarchy concept do exist, e.g., especially in the case of viral susceptibility to acids and alkalines [22], and exceptions are not uncommon for certain other chemistries. The hierarchy concept was never applied specifically to physical inactivation approaches, nor should it be. The evidence for heat inactivation, UV inactivation, and gamma irradiation indicates differing rankings of susceptibility to these modalities. Envelope status and particle size do not, in each case, relate to susceptibility for inactivation by these physical approaches [22, 78, 79, 80].
The validity of the hierarchy concept
The accuracy and usefulness of a hierarchy concept can be improved if the model is broken into separate chemistries for non-enveloped viruses, since many viruses do exhibit a reliable and consistent trend of susceptibility for a specific type of chemical. Table 9 and Figure 2 provide a summary of the relative order of susceptibility for selected non-enveloped viruses under specific types of chemistry.
Chemical | Lower susceptibility | Medium susceptibility | Higher susceptibility |
---|---|---|---|
Ethanol | Animal parvovirus | Poliovirus | Murine norovirus |
Simian virus 40 | Foot and mouth disease virus | Rhinovirus | |
Hepatitis A virus | Human norovirus | Adenovirus 5 | |
Enterovirus 71 | Feline calicivirus | Rotavirus | |
Adenovirus 2, 8 | |||
Isopropanol | Animal parvovirus | Adenovirus 5, 8 | Simian virus 40 |
Hepatitis A virus | Murine norovirus | Rotavirus | |
Enterovirus 71 | |||
Poliovirus | |||
Feline calicivirus | |||
NaOCl | Porcine parvovirus | Minute virus of mice | Feline calicivirus |
Hepatitis A virus | Hepatitis A virus | Adenovirus | |
Poliovirus | Rotavirus | ||
Enterovirus 71 | |||
Murine norovirus | |||
H2O2 | Animal parvovirus | Poliovirus | Rhinovirus |
Hepatitis A virus | Murine norovirus | Feline calicivirus | |
Adenovirus | Rotavirus | ||
PAA | Animal parvovirus | Poliovirus | Feline calicivirus |
Hepatitis A virus | Murine norovirus | ||
Adenovirus | |||
QAC | Animal parvovirus | Feline calicivirus | Rotavirus |
Poliovirus | Murine norovirus | Rhinovirus | |
Adenovirus 8, 25 | Adenovirus 5 | Coxsackievirus A11 | |
Low pH | Minute virus of mice | Human parvovirus 4 | Feline calicivirus |
Hepatitis A virus | Rhinovirus | ||
Poliovirus | Foot and mouth disease virus | ||
Enterovirus 71 | Enterovirus EV-D68 | ||
Coxsackievirus A9 | Human parvovirus B19 | ||
Murine norovirus | |||
Rotavirus | |||
Reovirus | |||
High pH | Bovine viral diarrhea virus | Reovirus | Murine minute virus |
Simian virus 40 | Feline calicivirus | ||
Hepatitis A virus | Adenovirus | ||
Canine parvovirus | Rotavirus | ||
Poliovirus | Foot and mouth disease virus | ||
Murine norovirus | |||
Tulane virus | |||
Aldehydes | Porcine parvovirus | Minute virus of mice | Poliovirus |
Hepatitis A virus | |||
Feline calicivirus | |||
Adenovirus | |||
Reovirus | |||
Rotavirus |
Relative order of susceptibility of non-enveloped viruses to chemical inactivation.
Abbreviations used: H2O2, hydrogen peroxide; NaOCl, sodium hypochlorite; PAA, peracetic acid; QAC, quaternary ammonium compound.
Relative order of susceptibility of non-enveloped viruses per microbicidal chemistry. Note: various types of adenoviruses exhibit different degrees of susceptibility to ethanol and quaternary ammonium compounds.
The Spaulding concept of the hierarchy of susceptibility of pathogens to microbicidal inactivation, along with its modifications, has been widely influential. Multiple industries as well as regulatory agencies have adopted or referenced this concept to various degrees [9, 10, 81, 82]. The concept does provide a good tool for understanding the innate differences and trending of susceptibility among various types of pathogens. For the most part, the hierarchy is insightful and valuable. It is particularly helpful when a pathogen is newly emerged, and limited or no knowledge is yet available regarding its level of susceptibility to microbicides [83, 84]. In fact, the United States Environmental Protection Agency (U.S. EPA) and Centers for Disease Control and Prevention (U.S. CDC) use the hierarchy concept as the basis of the Emerging Viral Pathogen Guidance for Antimicrobial Pesticides and public hygiene [10, 82, 85, 86] specifically to deal with just such a possibility.
It should be cautioned, however, that the hierarchy concept is largely oversimplified and by no means perfect [87]. For viruses, although enveloped viruses are usually more susceptible than non-enveloped viruses, certain enveloped viruses such as bovine viral diarrhea virus can be less susceptible than some non-enveloped viruses (e.g., feline calicivirus) under certain chemistries (e.g., low pH and high pH).
The accuracy and applicability of the hierarchy concept are more complex and limited among non-enveloped viruses. The trending is highly dependent on the type of chemistry; and the size of the virion is not always a primary determinant of viral susceptibility among non-enveloped viruses. If a clearer and more consistent trending can be identified among non-enveloped viruses, albeit only specific to a given type of chemistry, the knowledge should be useful.
To generalize an order of susceptibility, for a specific chemistry, data from side-by-side studies wherein viruses are evaluated concurrently by the same test method and under the same conditions should, ideally, be used. When results from different studies are used, caution should be taken to exclude conditional or case-specific differences that result from the test methodology and/or condition. For instance, a surface (carrier) test may give different log10 reduction results than a suspension test of the same microbicide or formulation under certain situations [88]. For example, the data of Kindermann et al. [47] and Tyler et al. [31] indicate that sodium hypochlorite causes a higher log10 reduction value (LRV) when tested in a suspension test than in a surface test. On the other hand, glutaraldehyde has been found to cause similar log reduction in either methodology, while hydrogen peroxide causes higher LRV in the surface test, which is thought to be likely related to the consumption of hydrogen peroxide by the protein in the virus-suspending solution [31].
The organic soil load in which the challenge virus is suspended prior to inoculation can also impact the viral inactivation outcome, especially for oxidizers, alcohols, and QAC. It would be inaccurate or even misleading if a result from a light organic load (e.g., 5% animal serum or phosphate-buffered saline) were to be directly compared with a test that used a heavier organic load (e.g., 90% blood or 20% fecal suspension). Tung
Other testing conditions may also affect the reduction results. For instance, a higher contact temperature may work in the favor of the virucide under investigation, which may result in a higher log reduction. Nemoto et al. [56] reported that a 0.125% glutaraldehyde solution completely inactivated rotavirus after 10 min under ambient temperature, but not when evaluated on ice. The pH and other components in the product formulation could also affect the viral reduction outcome, presumably by activating the chemical and/or by a synergistic or additive effect between the pH and the active chemical [22, 39, 89]. The efficacy of formulated versus non-formulated microbicides may differ even within the same type and concentration of active(s). For example, formulated QAC and ethanol products have been reported to exhibit strong activities against certain non-enveloped viruses albeit the efficacy may be weaker for non-formulated solutions [45, 54, 90, 91]. Therefore, the formulation of the microbicidal active must be considered. The viral stock (i.e., inoculum) preparation method and the challenge viral titer may also affect the reported viral reduction efficacy. For example, purified virus may be more susceptible than crude virus preparations [49]; viral clumps can make the virus less susceptible [92]; and a higher viral challenge titer could make the chemical harder to achieve an expected log10 reduction. Sometimes, viruses propagated in different host cell types may behave differently. It would therefore be ideal if all studies could use a standardized viral preparation and infectivity assay protocol. This is, of course, practically challenging. Last, but not least, the method for preparing the microbicide and the verification of the active concentration might also differ from lab to lab, thus potentially influencing the efficacy results obtained.
Despite these practically hard-to-avoid differences in test methodology and conditions, some generalizations on the pattern of susceptibility among non-enveloped viruses can still be made with confidence. For instance, it is quite apparent that the
The family
Different types of adenoviruses seem to exhibit varying degrees of susceptibility to ethanol and QAC. For example, adenovirus type 5 appears to be notably more susceptible to ethanol than are adenovirus types 2 and 8. In general, however, adenoviruses are more susceptible than many other non-enveloped viruses. Considering that adenovirus type 5 is listed as one of the allowable challenge viruses for a generic or “broad-spectrum” virucidal efficacy claim (i.e., a product that is effective for adenovirus type 5 may be considered effective against all viruses) [97, 98], this practice may not represent a challenge and lead to an insufficient safety margin, which is not supported by the published data.
Parvoviruses are among the smallest of non-enveloped viruses. The animal parvoviruses (e.g., minute virus of mice, porcine parvovirus, bovine parvovirus, canine parvovirus, etc.) are considered to exhibit very low susceptibility to chemical inactivation [99] and are commonly used as a worst-case model for viral inactivation studies. This literature review generally supports this notion, although it should be noted that the animal parvoviruses do not appear to represent a worst-case challenge for high-pH inactivation, and porcine parvovirus seems less susceptible than minute virus of mice at times. Additionally, human parvovirus B19 seems especially susceptible to acid treatment [100].
It has been observed that the particle size of a virus is not an exclusive or even a primary determinant of susceptibility to microbicides for non-enveloped viruses, albeit this characteristic may play a role. There are numerous reports demonstrating that larger non-enveloped viruses, such as adenoviruses and reoviruses, are less susceptible than some of the smaller non-enveloped viruses for certain chemistries. Interestingly though, rotavirus, a large non-enveloped virus, indeed seems to be the most susceptible among non-enveloped viruses, except to low pH.
The mechanisms underlying the large variation in susceptibility among non-enveloped viruses and the chemistry dependency are not always clear, but they could presumably be related to the physicochemical properties of the virus as well as the mechanisms of action of the chemical inactivants. For alcohols, for instance, it has been proposed that the hydrophobicity or hydrophilicity of the viral particles is an important determinant of susceptibility [101]. Poliovirus, which is hydrophilic, is more susceptible to ethanol than it is to isopropyl alcohol. This is attributed to the fact that ethanol is more hydrophilic than isopropanol. In comparison, the hydrophobic simian virus 40 is susceptible to isopropanol but not to ethanol [101]. Enterovirus 71 (EV71) and enterovirus EV-D68 (EV-D68) are both enteroviruses in the family
A review of the relative order of susceptibility for non-enveloped viruses under each chemistry reveals that the order for some chemicals (e.g. aldehydes) seems to fit the traditional hierarchy concept well (e.g., parvoviruses are less susceptible than larger viruses); but the order for some other chemistries (e.g., low pH) does not seem to agree with the concept as well.
The variability in viral susceptibility to physical treatments is not covered in this chapter; however, a marked degree of variation also exists for physical treatments, both within non-enveloped viruses and between enveloped and non-enveloped viruses [12, 16, 21, 49]. A comparison of the order of susceptibility of viruses to chemical versus physical treatments and an exploration of the underlying mechanisms would be interesting and revealing.
This chapter reviewed the literature on chemical inactivation of non-enveloped viruses, with an emphasis on the relative difference and trending of susceptibility among some relevant (from a public health perspective) non-enveloped viruses under each type of chemistry. The traditional concept of a hierarchy of susceptibility to microbicides provides a useful tool in understanding and predicting the susceptibility of a pathogen; however, the concept tends to be oversimplified. The order of susceptibility among non-enveloped viruses depends on the type of chemistry, and there is no universal order that holds true for all types of chemistries. Picornaviruses and caliciviruses exhibit a particularly high degree of intrafamily variation, and the order may even be reversed between viruses, depending on the chemistry. Additionally, larger non-enveloped viruses are not always more susceptible than some of the smaller non-enveloped viruses. It may be inappropriate to consider adenovirus type 5 as a worst-case non-enveloped virus; and even the animal parvoviruses, universally considered among the least susceptible to chemical inactivation, do not actually represent the least susceptible virus type for certain chemistries.
The author thanks Drs. Raymond Nims and M. Khalid Ijaz for the critical review of the manuscript and discussion.
The author declares no conflict of interest.
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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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Through comparative analysis, the chapter investigates sustainability potential of vernacular architecture in the region to derive core concepts as guidelines of reproducing the characteristics of society and reveal identity of contemporary architecture in the Arab World.",book:{id:"8260",slug:"urban-and-architectural-heritage-conservation-within-sustainability",title:"Urban and Architectural Heritage Conservation within Sustainability",fullTitle:"Urban and Architectural Heritage Conservation within Sustainability"},signatures:"Maha Salman",authors:[{id:"258226",title:"Dr.",name:"Maha",middleName:null,surname:"Salman",slug:"maha-salman",fullName:"Maha Salman"}]},{id:"51000",doi:"10.5772/63726",title:"Towards Sustainable Sanitation in an Urbanising World",slug:"towards-sustainable-sanitation-in-an-urbanising-world",totalDownloads:3202,totalCrossrefCites:11,totalDimensionsCites:17,abstract:"Urban sanitation in low‐ and middle‐income countries is at an inflection point. It is increasingly acknowledged that conventional sewer‐based sanitation cannot be the only solution for expanding urban areas. There are other objective reasons apart from the lack of capital. The lack of stable energy supplies, of spare parts and of human resources for reliable operation, and the increasing water scarcity are factors that seriously limit the expansion of centralised systems. This chapter argues that a new paradigm for urban sanitation is possible, if the heterogeneity within developing cities is reflected in the implementation of different sanitation systems, adapted to each urban context and integrated under one institutional roof. This new paradigm entails: (1) innovative management arrangements; (2) increased participation and the integration of individual, community and private sector initiatives; (3) thinking at scale to open new opportunities; (4) improved analysis of the situation and awareness raising. Moving beyond conventional approaches towards sustainable urbanisation needs to follow both a top‐down and a bottom‐up approach, with proper incentives and a variety of sanitation systems which, in a future perspective, will become part of the ‘urban ecosystem’.",book:{id:"5235",slug:"sustainable-urbanization",title:"Sustainable Urbanization",fullTitle:"Sustainable Urbanization"},signatures:"Philippe Reymond, Samuel Renggli and Christoph Lüthi",authors:[{id:"181079",title:"Dr.",name:"Christoph",middleName:null,surname:"Lüthi",slug:"christoph-luthi",fullName:"Christoph Lüthi"},{id:"182136",title:"Mr.",name:"Philippe",middleName:null,surname:"Reymond",slug:"philippe-reymond",fullName:"Philippe Reymond"},{id:"182137",title:"Mr.",name:"Samuel",middleName:null,surname:"Renggli",slug:"samuel-renggli",fullName:"Samuel Renggli"}]},{id:"42926",doi:"10.5772/55736",title:"Disaster Risk Management and Social Impact Assessment: Understanding Preparedness, Response and Recovery in Community Projects",slug:"disaster-risk-management-and-social-impact-assessment-understanding-preparedness-response-and-recove",totalDownloads:10044,totalCrossrefCites:3,totalDimensionsCites:11,abstract:null,book:{id:"3364",slug:"environmental-change-and-sustainability",title:"Environmental Change and Sustainability",fullTitle:"Environmental Change and Sustainability"},signatures:"Raheem A. Usman, F.B. Olorunfemi, G.P. Awotayo, A.M. Tunde and\nB.A. Usman",authors:[{id:"156875",title:"Dr.",name:"Usman A",middleName:null,surname:"Raheem",slug:"usman-a-raheem",fullName:"Usman A Raheem"},{id:"166449",title:"Dr.",name:"A.M",middleName:null,surname:"Tunde",slug:"a.m-tunde",fullName:"A.M Tunde"},{id:"167886",title:"Dr.",name:"F.B.",middleName:null,surname:"Olorunfemi",slug:"f.b.-olorunfemi",fullName:"F.B. Olorunfemi"},{id:"167887",title:"Dr.",name:"G.P.",middleName:null,surname:"Awotayo",slug:"g.p.-awotayo",fullName:"G.P. Awotayo"}]},{id:"44263",doi:"10.5772/54339",title:"Conservation and Sustainability of Mexican Caribbean Coral Reefs and the Threats of a Human-Induced Phase-Shift",slug:"conservation-and-sustainability-of-mexican-caribbean-coral-reefs-and-the-threats-of-a-human-induced-",totalDownloads:2352,totalCrossrefCites:4,totalDimensionsCites:11,abstract:null,book:{id:"3364",slug:"environmental-change-and-sustainability",title:"Environmental Change and Sustainability",fullTitle:"Environmental Change and Sustainability"},signatures:"José D. Carriquiry, Linda M. Barranco-Servin, Julio A. Villaescusa,\nVictor F. Camacho-Ibar, Hector Reyes-Bonilla and Amílcar L. Cupul-\nMagaña",authors:[{id:"158136",title:"Prof.",name:"Jose D.",middleName:"D.",surname:"Carriquiry",slug:"jose-d.-carriquiry",fullName:"Jose D. Carriquiry"},{id:"160078",title:"Dr.",name:"Julio A.",middleName:null,surname:"Villaescusa",slug:"julio-a.-villaescusa",fullName:"Julio A. Villaescusa"},{id:"160079",title:"MSc.",name:"Linda M.",middleName:null,surname:"Barranco-Servin",slug:"linda-m.-barranco-servin",fullName:"Linda M. Barranco-Servin"},{id:"160082",title:"Prof.",name:"Victor F.",middleName:null,surname:"Camacho-Ibar",slug:"victor-f.-camacho-ibar",fullName:"Victor F. Camacho-Ibar"},{id:"167394",title:"Dr.",name:"Hector",middleName:null,surname:"Reyes-Bonilla",slug:"hector-reyes-bonilla",fullName:"Hector Reyes-Bonilla"},{id:"167395",title:"Dr.",name:"Amilcar L.",middleName:null,surname:"Cupul-Magaña",slug:"amilcar-l.-cupul-magana",fullName:"Amilcar L. Cupul-Magaña"}]}],mostDownloadedChaptersLast30Days:[{id:"64381",title:"Sustainability and Vernacular Architecture: Rethinking What Identity Is",slug:"sustainability-and-vernacular-architecture-rethinking-what-identity-is",totalDownloads:4432,totalCrossrefCites:8,totalDimensionsCites:22,abstract:"Sustainability has often been a fundamental part of the composition of both tangible and intangible cultural resources; sustainability and preservation of cultural identity are complementary. Elements of sustainable design are integral to vernacular architecture that have evolved over time using local materials and technology emerging from ambient natural and cultural environment creating optimum relationships between people and their place. This chapter aims to redefine what identity is as a concept and the impact of globalization on contemporary architecture especially on regions with rich heritage and unique culture as the Arab World. To accomplish this, the chapter examines the emergence of “local identity” as a reaction to the globalization of cultural values, uniform architectural styles, and stereotype patterns through discussing sustainability as a motivation for identity in culture and architecture. The research methodology is based on conducting a qualitative analysis of literature review to the main concepts discussed in this chapter such as: identity, culture, vernacular architecture, and sustainability. Through comparative analysis, the chapter investigates sustainability potential of vernacular architecture in the region to derive core concepts as guidelines of reproducing the characteristics of society and reveal identity of contemporary architecture in the Arab World.",book:{id:"8260",slug:"urban-and-architectural-heritage-conservation-within-sustainability",title:"Urban and Architectural Heritage Conservation within Sustainability",fullTitle:"Urban and Architectural Heritage Conservation within Sustainability"},signatures:"Maha Salman",authors:[{id:"258226",title:"Dr.",name:"Maha",middleName:null,surname:"Salman",slug:"maha-salman",fullName:"Maha Salman"}]},{id:"67342",title:"Introductory Chapter: Heritage Conservation - Rehabilitation of Architectural and Urban Heritage",slug:"introductory-chapter-heritage-conservation-rehabilitation-of-architectural-and-urban-heritage",totalDownloads:2610,totalCrossrefCites:3,totalDimensionsCites:6,abstract:null,book:{id:"8260",slug:"urban-and-architectural-heritage-conservation-within-sustainability",title:"Urban and Architectural Heritage Conservation within Sustainability",fullTitle:"Urban and Architectural Heritage Conservation within Sustainability"},signatures:"Kabila Faris Hmood",authors:[{id:"214741",title:"Prof.",name:"Dr. Kabila",middleName:"Faris",surname:"Hmood",slug:"dr.-kabila-hmood",fullName:"Dr. Kabila Hmood"}]},{id:"76898",title:"The Relationship between Land Use and Climate Change: A Case Study of Nepal",slug:"the-relationship-between-land-use-and-climate-change-a-case-study-of-nepal",totalDownloads:695,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Land Use and Climate change are interrelated to each other. This change influences one another at various temporal and spatial scales; however, improper land uses are the primary causal factor on climate change. It studies relevant literature and Nepal’s case to assess the relationship between land use and climate change. Similarly focuses on how land-use impacts climate change and vice versa. In recent centuries land-use change significant effects on ecological variables and climate change. Likewise, understanding the research on both topics will help decision-makers and conservation planners manage land and climate.",book:{id:"10754",slug:"the-nature-causes-effects-and-mitigation-of-climate-change-on-the-environment",title:"The Nature, Causes, Effects and Mitigation of Climate Change on the Environment",fullTitle:"The Nature, Causes, Effects and Mitigation of Climate Change on the Environment"},signatures:"Pawan Thapa",authors:[{id:"349566",title:"M.Sc.",name:"Pawan",middleName:null,surname:"Thapa",slug:"pawan-thapa",fullName:"Pawan Thapa"}]},{id:"50282",title:"Relation Between Land Use and Transportation Planning in the Scope of Smart Growth Strategies: Case Study of Denizli, Turkey",slug:"relation-between-land-use-and-transportation-planning-in-the-scope-of-smart-growth-strategies-case-s",totalDownloads:4663,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"In the decision-making process of planning residential areas in developing countries, importance of the commercial areas and need for a sustainable urban transportation infrastructure have generally been ignored based on several sociopolitical reasons. Meanwhile, decision-making periods of location choice and determining areal densities are conducted without quantitative spatial/technical analyses. Those urban matters bring along new planning paradigms like smart growth (SG) and new urbanism. SG is a land use planning paradigm which indicates that traffic problems should be minimized by transit alternatives, effective demand management and providing a balance between land use and transportation planning. This study aims to apply SG strategies to the land use planning process and evaluate the accuracy of land use planning decisions in the perspective of sustainable transportation. In order to reveal the effects of land use planning decisions on the available transportation infrastructure, two scenarios are investigated for 2030. In the first scenario “do nothing” option is considered, while the residential area densities and trip generation rates are regulated based on SG strategies in the second scenario. The results showed that the land use and traffic impact analyses should simultaneously be conducted before land use configuration process.",book:{id:"5235",slug:"sustainable-urbanization",title:"Sustainable Urbanization",fullTitle:"Sustainable Urbanization"},signatures:"Gorkem Gulhan and Huseyin Ceylan",authors:[{id:"182126",title:"Dr.",name:"Gorkem",middleName:null,surname:"Gulhan",slug:"gorkem-gulhan",fullName:"Gorkem Gulhan"},{id:"185555",title:"Dr.",name:"Huseyin",middleName:null,surname:"Ceylan",slug:"huseyin-ceylan",fullName:"Huseyin Ceylan"}]},{id:"42926",title:"Disaster Risk Management and Social Impact Assessment: Understanding Preparedness, Response and Recovery in Community Projects",slug:"disaster-risk-management-and-social-impact-assessment-understanding-preparedness-response-and-recove",totalDownloads:10040,totalCrossrefCites:3,totalDimensionsCites:11,abstract:null,book:{id:"3364",slug:"environmental-change-and-sustainability",title:"Environmental Change and Sustainability",fullTitle:"Environmental Change and Sustainability"},signatures:"Raheem A. Usman, F.B. Olorunfemi, G.P. Awotayo, A.M. Tunde and\nB.A. Usman",authors:[{id:"156875",title:"Dr.",name:"Usman A",middleName:null,surname:"Raheem",slug:"usman-a-raheem",fullName:"Usman A Raheem"},{id:"166449",title:"Dr.",name:"A.M",middleName:null,surname:"Tunde",slug:"a.m-tunde",fullName:"A.M Tunde"},{id:"167886",title:"Dr.",name:"F.B.",middleName:null,surname:"Olorunfemi",slug:"f.b.-olorunfemi",fullName:"F.B. Olorunfemi"},{id:"167887",title:"Dr.",name:"G.P.",middleName:null,surname:"Awotayo",slug:"g.p.-awotayo",fullName:"G.P. Awotayo"}]}],onlineFirstChaptersFilter:{topicId:"136",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82644",title:"Climate-Driven Temporary Displacement of Women and Children in Anambra State, Nigeria: The Causes and Consequences",slug:"climate-driven-temporary-displacement-of-women-and-children-in-anambra-state-nigeria-the-causes-and-",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.104817",abstract:"With increasing periods of extreme wet seasons, low lying geographic position, with socioeconomic, and political factors; some communities in Anambra State, Nigeria experience heightened floods annually resulting in loss of shelter, displacement of people with breakdown of livelihoods, particularly in rural communities worsening their risks and vulnerabilities. In 2012, a major flood event in the state temporarily displaced about 2 million people. In this chapter, we used a community-based adaptation approach to investigate the causes and consequences of climate-related temporary displacement on community members in Ogbaru LGA, Anambra State following flood events. We used global positioning system to obtain the community’s ground control points and gathered our data via field observation, transects walks, focus group discussions, photography, and in-depth interviews. Our findings reveal a heightened magnitude of flood related disasters with decreased socio-economic activities, affecting their health and well-being. Also, the community members have a practice of returning to their land, after flood events, as a local mitigating risk management strategy. For multilevel humanitarian responses at the temporary shelter camps, it becomes imperative to meaningfully engage the community members on the challenging risks and vulnerabilities they experience following climate-driven temporary displacement to inform adaptation and resilience research, policy change and advocacy.",book:{id:"7724",title:"Climate Change in Asia and Africa - Examining the Biophysical and Social Consequences, and Society's Responses",coverURL:"https://cdn.intechopen.com/books/images_new/7724.jpg"},signatures:"Akanwa Angela Oyilieze, Ngozi N. Joe-Ikechebelu, Ijeoma N. Okedo-Alex, Kenebechukwu J. Okafor, Fred A. Omoruyi, Jennifer Okeke, Sophia N. Amobi, Angela C. Enweruzor, Chinonye E. Obioma, Princess I. Izunobi, Theresa O. Nwakacha, Chinenye B. Oranu, Nora I. Anazodo, Chiamaka A. Okeke, Uwa-Abasi E. Ugwuoke, Uche M. Umeh, Emmanuel O. Ogbuefi and Sylvia T. Echendu"},{id:"79637",title:"Evaluation of the Spatial Distribution of the Annual Extreme Precipitation Using Kriging and Co-Kriging Methods in Algeria Country",slug:"evaluation-of-the-spatial-distribution-of-the-annual-extreme-precipitation-using-kriging-and-co-krig",totalDownloads:53,totalDimensionsCites:0,doi:"10.5772/intechopen.101563",abstract:"In this chapter, we have conducted a statistical study of the annual extreme precipitation (AMP) for 856 grid cells and during the period of 1979–2012 in Algeria. In the first step, we compared graphically the forecasts of the three parameters of the generalized extreme value (GEV) distribution (location, scale and shape) which are estimated by the Spherical model. We used the Cross validation method to compare the two methods kriging and Co-kriging, based on the based on some statistical indicators such as Mean Errors (ME), Root Mean Square Errors (RMSE) and Squared Deviation Ratio (MSDR). The Kriging forecast error map shows low errors expected near the stations, while co-Kriging gives the lowest errors on average at the national level, which means that the method of co-Kriging is the best. From the results of the return periods, we calculate that after 50 years the estimated of the annual extreme precipitation will exceed the maximum AMP is observed in the 33-year.",book:{id:"7724",title:"Climate Change in Asia and Africa - Examining the Biophysical and Social Consequences, and Society's Responses",coverURL:"https://cdn.intechopen.com/books/images_new/7724.jpg"},signatures:"Hicham Salhi"},{id:"77854",title:"Flooding and Flood Modeling in a Typhoon Belt Environment: The Case of the Philippines",slug:"flooding-and-flood-modeling-in-a-typhoon-belt-environment-the-case-of-the-philippines",totalDownloads:160,totalDimensionsCites:0,doi:"10.5772/intechopen.98738",abstract:"Flooding is a perennial world-wide problem and is a serious hazard in areas where the amount of precipitable water has potential to dump excessive amount of water. The warming of the Earth’s climate due to the increase in greenhouse gases (GHGs) increases the availability of water vapor and hence, of extreme precipitation as observed and forecasted by researchers. With rainfall intensity too high, the torrential rains coupled with weather systems that enhances its effects, flooding not only submerges anything low-lying, it also washes away living and non-living things along the course of the river and the floodplain. The flooding is even worsened by the increase in velocity of flow caused by unsustainable urbanization and denudation of the watershed at the headwaters. Nature’s strength is an order of a magnitude that is way beyond that of the strength of men but human ingenuity enables us to transform our living environment into models that could help us better understand it. Flood modeling provides us decision support tools to deal better with nature. It also enables us to simulate the future especially nowadays that changes in our climate is imminent and even happening already in many parts of the world. Therefore, strategies on how to cope with our ever changing environment is very important particularly to countries that are at more risk to climate change such as the archipelagic Philippines.",book:{id:"7724",title:"Climate Change in Asia and Africa - Examining the Biophysical and Social Consequences, and Society's Responses",coverURL:"https://cdn.intechopen.com/books/images_new/7724.jpg"},signatures:"Fibor J. Tan"},{id:"77797",title:"Adapting to Climatic Extremes through Climate Resilient Industrial Landscapes: Building Capacities in the Southern Indian States of Telangana and Andhra Pradesh",slug:"adapting-to-climatic-extremes-through-climate-resilient-industrial-landscapes-building-capacities-in",totalDownloads:98,totalDimensionsCites:0,doi:"10.5772/intechopen.98732",abstract:"There is now greater confidence and understanding of the consequences of anthropogenic caused climate change. One of the many impacts of climate change, has been the occurrence of extreme climatic events, recent studies indicate that the magnitude, frequency, and intensity of hydro-meteorological events such as heat waves, cyclones, droughts, wildfires, and floods are expected to increase several fold in the coming decades. These climatic extremes are likely to have social, economic, and environmental costs to nations across the globe. There is an urgent need to prepare various stakeholders to these disasters through capacity building and training measures. Here, we present an analysis of the capacity needs assessment of various stakeholders to climate change adaptation in industrial parks in two southern states of India. Adaptation to climate change in industrial areas is an understudied yet highly urgent requirement to build resilience among stakeholders in the Indian subcontinent. The capacity needs assessment was conducted in two stages, participatory rural appraisal (PRA) and focus group discussion (FGD) were conducted among various stakeholders to determine the current capacities for climate change adaptation (CCA) for both, stakeholders and functional groups. Our analysis indicates that in the states of Telangana and Andhra Pradesh, all stakeholder groups require low to high levels of retraining in infrastructure and engineering, planning, and financial aspects related to CCA. Our study broadly supports the need for capacity building and retraining of functionaries at local and state levels in various climate change adaptation measures; likewise industry managers need support to alleviate the impacts of climate change. Specific knowledge, skills, and abilities, with regard to land zoning, storm water management, developing building codes, green financing for CCA, early warning systems for climatic extremes, to name a few are required to enhance and build resilience to climate change in the industrial landscapes of the two states.",book:{id:"7724",title:"Climate Change in Asia and Africa - Examining the Biophysical and Social Consequences, and Society's Responses",coverURL:"https://cdn.intechopen.com/books/images_new/7724.jpg"},signatures:"Narendran Kodandapani"},{id:"77460",title:"Changing Climatic Hazards in the Coast: Risks and Impacts on Satkhira, One of the Most Vulnerable Districts in Bangladesh",slug:"changing-climatic-hazards-in-the-coast-risks-and-impacts-on-satkhira-one-of-the-most-vulnerable-dist",totalDownloads:210,totalDimensionsCites:0,doi:"10.5772/intechopen.98623",abstract:"Changes in the climate due to anthropogenic and natural variation are indicated by parameters including temperature and rainfall. Climate change variability with changing trends of the two have been unpredictable and unprecedented globally leading to changing weather patterns, natural disasters, leading to sectoral impacts on food and water security, livelihood, human health among others. This research analyses the changing patterns of these parameters over the last 35/37 years of Satkhira district of Bangladesh to assess the state and trend across spatial and temporal dimensions. Such, the study validates to rationalize the observed seasonal changes that persist in Satkhira of Bangladesh. Both in terms of intensity and frequency of the occurrences of natural disasters, the series of natural events have been triangulated, with impacts and vulnerability being assessed from temperature variations, erratic rainfall, cyclone, flood and water logging etc. The study’s prime contribution remains in attribution of climate change in relation contextual circumstances in the region including sea level rise, salinity intrusion. Therefore, the risk and climatic hazards and its resulting impacts over time has been assessed to draw deeper connection between theoretical and practical values. The series of analyses also draw conclusion that assets are at risk from changing climatic condition.",book:{id:"7724",title:"Climate Change in Asia and Africa - Examining the Biophysical and Social Consequences, and Society's Responses",coverURL:"https://cdn.intechopen.com/books/images_new/7724.jpg"},signatures:"Md. Golam Rabbani, Md. Nasir Uddin and Sirazoom Munira"},{id:"76915",title:"The Impacts of Climate Change in Lwengo, Uganda",slug:"the-impacts-of-climate-change-in-lwengo-uganda",totalDownloads:100,totalDimensionsCites:0,doi:"10.5772/intechopen.97279",abstract:"Climate Change has become a threat worldwide. Vulnerable communities are at foremost risk of repercussions of climate change. The present study aimed at highlighting a case study of climate change impacts on Lwengo District of Uganda. Out of the total geographical area of the district, 85% hectares are under cultivation and most of its population depends majorly on the rain- fed agriculture sector to meet the food requirement and as a major income source. With the changing climatic conditions, agriculture is the major sector which is being impacted. The region has experienced disasters from some time, usually the second seasons rains used to result in such disasters but since 2016 both seasons have occurred disasters, which majorly include hailstorm, strong wind, long dry spells, pests and diseases. The situation became more severe due to shortage of availability of skilled human resources, quality equipment for disaster management, limited financial resources and weak institutional capacity, which resulted in increasing vulnerability of small farm holders. Some of the adaptation strategies are being taken up by the government but there is a need to understand prospects of decision-making that are site specific and more sustainable for smallholder communities. Climatic changes possess many obstacles to farming communities which require sustainable adaptation to enhance the adaptive capacities of the communities through continued production systems, which are more resilient to the vagaries of weather. Farmers are practising such options which are location specific, governed by policy framework and dependent on dynamism of farmers. 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He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",slug:"cecilia-cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",slug:"gil-goncalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",slug:"johann-f.-osma",fullName:"Johann F. 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